Convenient synthesis of sulfated oligofucosides

Article abstract of DOI:10.1016/j.carres.2010.04.006

Two types of sulfated octyl tetra- to octaoligofucosides with different sulfation patterns were synthesized employing a combination of stepwise elongation and convergent strategies in which trichloroacetimidates and thioglycosides were selected as the glycosyl donors.

Full text of DOI:10.1016/j.carres.2010.04.006

Carbohydrate Research 345 (2010) 1522–1532
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Convenient synthesis of sulfated oligofucosides
Chengli Zong a, Zhongzhen Li a, Tiantian Sun a, Peng Wang a, Ning Ding b, Yingxia Li a,b,
*
a School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
b School of Pharmacy, Fudan University, Shanghai 201203, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Two types of sulfated octyl tetra- to octaoligofucosides with different sulfation patterns were synthesized
employing a combination of stepwise elongation and convergent strategies in which trichloroacetimi-
dates and thioglycosides were selected as the glycosyl donors.
Received 12 February 2010
Received in revised form 3 April 2010
Accepted 8 April 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Available online 11 April 2010
Keywords:
Sulfated oligofucoside
Stepwise elongation
Convergent strategy
Synthesis
1. Introduction
terpart based on Sarcoma 180 and Lewis lung carcinoma model
studies, indicating the importance of the presence of sulfate
Sulfated fucans, polysaccharides containing substantial per-
groups. Its antitumor activity was achieved by direct cytotoxic ef-
fects (through induction of apoptosis) and induced immune re-
sponses,8 while fucans were also shown to inhibit metastasis by
inhibiting angiogenesis13 and the interaction between carcinoma
cells and platelets.14
centages of L-fucose and sulfated ester groups, are constituents of
brown algae and some marine invertebrates.1,2 These polysaccha-
rides possess a wide variety of structures that vary from simple fu-
can sulfates to complex heteropolysaccharides. However most of
them have regular
a-
L-(1?3)- and/or
a
-L
-(1?4)-linked
L
-fucopyr-
To further probe the relationship of pattern of sulfation and
anosyl repeating units.3 Recently, fucans have been reported to
show a wide spectrum of biological and physiological activities
such as anticoagulant and antithrombotic activities,4,5 blocking
virus infection,6 as well as anti-tumor and anti-inflammatory activ-
ities.7,8 Thus fucans may have a potential application as drugs or
functional food and biological materials with few side effects. At
this time almost nothing is known about how their conformations
or regular spatial patterns of sulfate groups determine their biolog-
ical properties due to their structural complexity and heterogene-
ity.9,10 Therefore, there is an urgent need to synthesize oligofucans
with specific structures to elucidate the structure–activity
relationships.
length of a-L-(1?3)-linked oligofucans with bioactivities such as
antitumor activity, we designed and synthesized linear partially
sulfated tetra- to octaoligofucosides 1–8. As shown in Figure 1, be-
sides even-numbered oligofucans, odd-numbered ones were also
synthesized. Different from the octyl b-glycosylic bond12,15 at the
reducing end, the a-L-linkage was successfully introduced. And in
the synthesis, thioglycosides and trichloroacetimidates were se-
lected as donors, and stepwise elongation combined with conver-
gent strategy was applied with great convenience.
2. Results and discussion
Until now, only Nifantiev and co-workers11 and Du and
As for the synthetic approaches of the a-L-(1?3)-linked oligofu-
co-workers12 have reported the synthesis of some
a-(1?3)-linked
oligofucans. The former synthesized linear even-numbered 2-sul-
fated tetra-, hexa-, octasaccharides, and a 4-sulfated tetrasaccha-
cans construction, Nifantiev and co-workers employed [2+2],
[2+4], and [4+4] carbohydrate skeleton assembly strategies for
the synthesis of tetra-, hexa-, and octasaccharides with trichloro-
acetimidates as glycosyl donors. With b-configured octyl as the
reducing-end modification, Du and co-workers applied stepwise
elongation in the formation of the tetrasaccharide with a thiogly-
coside as the donor. Encouraged by these accomplishments and
considering the structures of the designed partially sulfated tetra-
to octa-oligofucosides 1–8, we decided to apply a [2+2] assembling
strategy for the assembly of the tetrasaccharide and an [n+1]
ride. The latter reported the synthesis of
a (1?3)-linked
tetrasaccharide and its fully sulfated derivative, and corresponding
bioassay data suggested that the sulfated fucose oligomer showed
more potent antitumor activities than that of its unsulfated coun-
* Corresponding author. Tel./fax: +86 21 51980127.
E-mail address: liyx417@fudan.edu.cn (Y. Li).
0008-6215/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2010.04.006

C. Zong et al. / Carbohydrate Research 345 (2010) 1522–1532
1523
OC8H17
R1
R1
H
R2
H
R2
R3
H
R3
O
O
n
1
2
3
4
5
n
1
2
3
OR1
OR2
O
O
SO3Na
SO3Na
SO3Na
SO3Na
SO3Na
1
2
3
4
5
6
7
8
SO3Na
SO3Na
SO3Na
SO3Na
SO3Na
SO3Na
OR1
OR2
O
O
H
n
H
H
OR1
H
H
H
OR2
O
OR1
H
H
OR3
OR2
H
H
Figure 1. Sulfated tetra- to octa-oligofucosides 1–8.
strategy for the construction of the penta- to octasaccharides with
trichloroacetimidate and thioglycoside as donors.
the 2-O- and terminal 3-, 4-O-sulfo derivatives. Block 11 as a thio-
glycoside, which either permitted its precursor 10 as a glycosyl
As shown in Scheme 1, partially sulfated tetra- to octa-oligofu-
cosides 1–8 were retrosynthetically disconnected into the minimal
repeating block 11, which contained a 4-O-benzoyl group that fa-
acceptor in the construction of a-L-(1?3)-linked glycosidic bond
or directly used as a glycosyl donor was chosen to construct the
tetrasaccharide. And because glycosyl acceptors were ‘disarmed’
due to the electron-withdrawing effect of the acyl groups in the
assembly of penta- to octa-saccharides, the more reactive trichlo-
roacetimidate 12 was prepared as the glycosyl donor instead of
thioglycoside 11.
vored the formation of the a-L-configuration due to its remote par-
ticipation effect,11 a 3-O-acetyl group that could be selectively
removed under mild acid conditions for further elongation and a
2-O-benzyl protecting group that distinguished 2-OH from the
other hydroxyl groups. Such an arrangement of protecting groups
permitted the use of one common precursor for the synthesis of
The synthesis of 11(b) was reported by Sarkar and Roy16 start-
ing from ethyl 1-thio-
a
,b-
L-fucopyranoside (9) in a total yield of
OC8H17
OR1
OC8H17
OBn
OC8H17
O
O
O
O
O
OBn
O
OC8H17
OR2
O
OBz
O
OBz
SEt
OBn
O
O
O
O
O
OBn
OR1
OBn
OBn
O
OBz
O
+
OBz
O
O
O
n
n
OR2
O
n
OBz
O
OBz
O
OBn
OBn
OR1
n+1
assembling
stradegy
OBn
OBn
2+2
assembling
stradegy
OH
OAc
OBz
O
OBz
O
O
OR2
O
OR3
OBz
O
OBz
O
OR1
OBn
OBn
OR2
n = 1−5
n=1-5
OAc
OH
OBz
n = 1−4
OBz
R1 = SO3Na, R2 = R3 = H
or R1 = H, R2 = R3 = SO3Na
OCNHCCl3
OBn
SEt
OBn
O
O
OAc
OBz
11
OAc
12
OBz
Scheme 1. Retrosynthetic analysis of target compounds.
OCNHCCl3
OBn
SEt
SEt
OH
SEt
OBn
O
b
O
O
O
SEt
OBn
c
O
a
OBn
OH
OH
O
OAc
OAc
OBz
OH
O
OBz
OBz
11 (α:β, 1:3)
9
10 (α:β, 1:3)
12
Ph
OEt
SEt
OBn
O
d
OAc
OBz
O
OC8H17
OBn
11 (β)
OAc
OBz
OCNHCCl3
e
13 (α:β, 1:1)
O
OBn
OAc
OBz
OBz
12
OC8H17
OC8H17
OBn
SEt
O
O
f
g
OBn
O
OBn
OAc
OH
OBz
OBz
OAc
14
13 (α only)
11 (α)
Scheme 2. Reagents and conditions: (a) (i) (EtO)3CPh, camphorsulfonic acid, CH3CN; (ii) NaH, DMF, BnBr; (iii) 1 M HCl, 72% for three steps; (b) Ac2O, Pyr, DMAP, 84%; (c) (i)
NBS, acetone–H2O, 78%; (ii) CCl3CN, DBU, DCM, rt, 79%; (d) C8H17OH, NIS/AgOTf or NIS/TfOH, 87%; (e) C8H17OH, TMSOTf or BF3ꢀEt2O, 85%; (f) C8H17OH, NIS, AgOTf, DCM–Et2O,
94%; (g) AcCl–MeOH, 76%.

1524
C. Zong et al. / Carbohydrate Research 345 (2010) 1522–1532
50% for five steps (Scheme 2). Protecting group manipulations are
tedious and lengthy. Here we simplified the preparation of 11 from
readily available 917 in a total yield of 60% for two one-pot steps as
was carried out smoothly with 4% acetyl chloride in methanol to
afford acceptor 14 (76%).
With monosaccharide donors and acceptors in hand, target tet-
rasaccharides 1 and 6 were prepared as shown in Scheme 3. Firstly,
disaccharide acceptor 16 and donor 17 were prepared. The remain-
ing b-configured 10 and 11 were used as the acceptor and donor,
respectively, to construct 15 and 17. Thus glycosylation of 11(b)
shown in Scheme 2. Compound 9 (a:b = 1:4) was first transformed
into the cyclic 3,4-O-orthobenzoate, which was followed by 2-O-
benzylation and regioselective ring opening of ortho ester by acidic
hydrolysis to afford 10.16 Subsequent acetylation of compound 10
gave donor 11 as an
a
/b mixture (
a
:b, 1:3). The mixture of anomers
and 14 was carried out to give the only a-L-(1?3)-linked disaccha-
could be separated by silica gel column chromatography to afford
the individual anomers. Then 12 was conveniently prepared from
11 in a yield of 62% (over two steps).
Using glycosyl donors with different reactivities, we tried the
construction of the octyl a-L-fucopyranoside. Glycosylation of 1-oct-
anol with donors 11(b) and 12 was carried out, respectively, under
the promotion of N-iodosuccinimide/silver trifluoromethanesulfo-
nate (NIS/AgOTf), N-iodosuccinimide/trifluoromethanesulfonic acid
(NIS/TfOH), trimethylsilyl trifluoromethanesulfonate (TMSOTf), or
boron trifluoride–ethyl ether complex (BF3ꢀEt2O). However,
compound 13 was always obtained along with its b-isomer. To our
ride 15 in a good yield (87%), which was very different from that of
the glycosylation of 11(b) with 1-octanol. Disaccharide acceptor 16
was obtained by deacetylation of 15 in a yield of 80%. Disaccharide
donor 17 was prepared by coupling 10(b) with 12 in the presence
of TMSOTf at ꢁ78 °C (74%).
Then tetrasaccharide was assembled via a [2+2] strategy. Cou-
pling of disaccharide acceptor 16 with donor 17 was carried out
smoothly to afford only
a-L-linked tetrafucoside 18 in a yield of
81%. Cleavage of all the benzyl groups in 18 was performed under
Pd/C-catalyzed hydrogenolysis conditions to give 19 in good yield
(80%). 2-O-Sulfonation of 19 with the sulfur trioxide–pyridine
complex in anhydrous DMF at rt was followed by the removal of
all benzoyl and acetyl groups with aqueous sodium hydroxide to
give target tetrasaccharide 1 (92%, for two steps).
delight when the
1:1 CH2Cl2–Et2O at 0 °C using NIS/AgOTf as the promotion system,
the desired -fucoside 13 was smoothly provided (94%). The ano-
a isomer of 11 was condensed with 1-octanol in
a
meric configuration of 13 was confirmed clearly by observation of
As for the preparation of tetrasaccharide 6, saponification of the
benzoyl and acetyl groups in 18 was first carried out to provide 21,
a 1H NMR doublet (J 3.7 Hz) at 4.82 ppm. Then deacetylation of 13
OC8H17
OC 8H17
OBn
OC8H17
OBn
:
R1 = SO3 Na, R2 = H, R3 = H;
R1 = SO3Na, R2 = Bz, R3 = Ac;
OC8H
OR1
1
17 g
O
O
O
OBn
O
O
O
a
O
SEt
OBn
b
20
:
O
OBz
O
OBz
O
OH
OR2
O
f
OAc
OBz
OBz
OR1
19: R1 = H, R2 = Bz, R3 = Ac;
18: R1 = Bn, R2 = Bz, R3 = Ac;
OBn
OBn
11 (β isomer)
14
OH
16
e
d
OAc
15
O
OR2
O
OBz
OBz
OR1
OR2
O
O
h
i
OCNHCCl3
OBn
SEt
OBn
21: R1 = Bn, R2 = R3 = H;
O
SEt
O
O
OBn
OR1
O
OR2
OH
OBz
OAc
OR3
22: R1 = Bn, R2 = R3 = SO3Na;
c
OBz
OBz
O
j
OBn
10 (β isomer)
12
1
: R = H, R2 = R3 = SO3Na;
OAc
6
OBz
17
Scheme 3. Reagents and conditions: (a) NIS, AgOTf, DCM–Et2O, 87%; (b) AcCl–MeOH, 80%; (c) TMSOTf, DCM, ꢁ78 °C, 74%; (d) NIS, AgOTf, DCM–Et2O, 81%; (e) Pd/C, H2, EtOAc–
EtOH, 55 °C, 12 h, 80%; (f) SO3ꢀPyr, DMF, rt, 1 h; (g) 0.4 N NaOH, 40 °C, 4 h, 92%; (h) MeONa–MeOH, 100%; (i) (i) SO3ꢀPyr, DMF, rt, 1 h; (ii) 3 N NaOH; (j) Pd/C, H2, MeOH–H2O,
72 h, 82%.
OC8H17
OBn
OC8H17
OBn
OC8H17
OBn
OC8H17
OH
OC8H17
O
O
O
O
O
O
O
O
O
O
OSO3Na
OBz
O
OBz
O
OBz
O
OBz
O
OH
O
OBn
OBn
OBn
OH
OSO3Na
n
n+1
n+1
d
n+1
O
n
a
O
O
c
O
O
b
OBz
O
OBz
O
OBz
O
OBz
O
OH
O
OBn
OBn
OBn
OH
OSO3Na
O
O
O
O
O
OBz
O
OBz
O
OBz
O
OBz
O
OH
O
OBn
OBn
OBn
OH
OSO3Na
OAc
OH
OAc
OAc
OH
OBz
n = 1
OBz
OBz
OBz
OH
18
27
23
24
27
28
31
32
2
3
n = 2
n = 3
n = 4
28
29
25
26
29
30
33
34
4
5
Scheme 4. Reagents and conditions: (a) AcCl–MeOH, 87% for 23, 77% for 24, 94% for 25, 92% for 26; (b)12, TMSOTf, DCM, -20 °C, (92% for 27, 88% for 28, 94% for 29, 64% for
30); (c) Pd/C, H2, EtOAc–EtOH, 55 °C, 12 h, (80% for 31, 85% for 32, 87% for 33, 80% for 34); (d) (i) SO3ꢀPyr, DMF, rt, 1 h; (ii) 0.4 N NaOH, 40 °C, 4 h, (92% for 2, 87% for 3, 83% for
4, 69% for 5).

C. Zong et al. / Carbohydrate Research 345 (2010) 1522–1532
1525
OC8H17
OBn
OC8H17
OBn
OC8H17
OH
O
O
O
O
O
O
OBz
O
OH
O
NaSO3O
O
O
OBn
OBn
OH
n
n
n
O
O
b
OBz
O
a
OH
O
NaSO3O
O
OBn
OBn
OH
O
O
O
OBz
O
OH
O
NaSO3 O
O
OBn
OBn
OH
OAc
OBz
OH
OSO3Na
OH
NaSO3O
n = 2
n = 3
24
25
35
36
7
8
Scheme 5. Reagents and conditions: (a) MeONa, MeOH–DCM, 40 °C, 72 h, 70% for 35, 78% for 36; (b) (i) SO3ꢀPyr, DMF, rt, 1 h; (ii) 3 N NaOH; (iii) Pd/C, H2, H2O–MeOH, 40 °C,
12 h, 89% for 7, 94% for 8.
which was treated with the sulfur trioxide–pyridine complex in
anhydrous DMF at rt. NaOH (3 N) was used to quench the reaction
and turn the product into a sodium salt. Then debenzylation with
Pd/C-catalyzed hydrogenolysis gave target tetrasaccharide 6 in a
yield of 82% (for three steps).
molecular sieves. The reaction mixture was stirred for 0.5 h at rt,
then cooled to 0 °C, and NIS (1.5 equiv) and AgOTf (0.1 equiv) were
added. The mixture was neutralized with Et3N and evaporated.
Flash column chromatography (silica gel) of the residue afforded
the product.
Synthesis of 2-sulfated pentasaccharide 2 was carried out
according to the [4+1] chain-assembly strategy as outlined in
Scheme 4. Selective acidic O-deacetylation of key intermediate
18 was first performed to prepare acceptor 23 in a yield of 87%.
As mentioned above, for longer oligosaccharide chain assembly,
the more reactive trichloroacetimidate 12 was needed, so 12 was
coupled with 23 in the presence of a catalytic amount of TMSOTf
to furnish 27 in a high yield of 92%. Then debenzylation of the fully
protected 27 afforded 31 in a yield of 80%, which was followed by
O-sulfonation, deacetylation, and debenzoylation to give target
pentaoligofucoside 2 in an excellent yield of 92% (for two steps).
Following a route similar to the one mentioned above, the syn-
thesis of 2-sulfated hexa- to octasaccharides 3, 4, and 5 was accom-
plished via an [n+1] chain-assembly strategy.
At last, the synthesis of the terminal 3- and 4-sulfated 7 and 8
was carried out as described in the preparation of 6 (Scheme 5).
In conclusion, two patterns of sulfated linear tetra- to octa-oli-
gofucans were synthesized employing a combination of trichloro-
acetimidate and thioglycoside glycosyl donors. Stepwise
elongation and convergent strategies were applied in the synthesis
as well. The biological studies of oligofucoidans 1–8 are under way
and will be published in due course.
3.2.2. Glycosylation employing trichloroacetimidate
To a solution of glycosyl donor (1.2 equiv) and glycosyl acceptor
(1.0 equiv) in anhyd CH2Cl2 with argon protection was added 4 Å
molecular sieve. The mixture was stirred for 0.5 h at rt and then
cooled to ꢁ20 °C or ꢁ78 °C, TMSOTf (0.1 equiv) was added. The
mixture was neutralized with Et3N and evaporated. Flash column
chromatography (silica gel) of the residue afforded the product.
3.2.3. Deacetylation employing acetyl chloride
To a solution of starting compound in anhyd CH2Cl2 (8 mL) was
added a mixture of AcCl (0.6 mL) and MeOH (15 mL), and the mix-
ture was kept at rt for 12 h. Then H2O (40 mL) was added, and the
mixture was extracted with CH2Cl2 (3 ꢂ 30 mL). The combined or-
ganic layer was dried (Na2SO4) and concentrated. Flash column
chromatography (silica gel) of the residue afforded the product.
3.2.4. Debenzylation employing Pd/C-catalyzed hydrogenolysis
To a solution of the protected oligosaccharide in 1:1 EtOAc–
EtOH was added 10% Pd/C (20 times the mass of the oligosaccha-
ride), the mixture was degassed, and the flask was filled with H2.
The mixture was stirred for 12 h at 55 °C. Pd/C was separated by
filtration through a Celite pad, and the filtrate was concentrated.
Flash column chromatography (silica gel) of the residue afforded
the product.
3. Experimental
3.1. General methods
3.3. Synthesis of octyl 3-O-acetyl-4-O-benzoyl-2-O-benzyl-a-L-
fucopyranoside (13)
Solvents were purified according to conventional procedures.
Thin-layer chromatography (TLC) was performed on precoated E.
Merck Silica Gel 60 F254 plates. Flash column chromatography
was performed on silica gel (200–300 mesh, Qingdao, China). Gel
chromatography was performed on SepHadex G-10 column
(2 ꢂ 20 cm) by elution with H2O at a flow rate of 1 mL/min. Optical
rotations were determined with a Perkin–Elmer Model 241 MC
polarimeter. 1H NMR and 13C NMR spectra were recorded on a JEOL
JNM-ECP 600 spectrometer. Mass spectra were recorded on a Q-
TOF Global mass spectrometer.
3.3.1. Ethyl 4-O-benzoyl-2-O-benzyl-1-thio-L-fucopyranoside
(10)
To a solution of 9 (3.0 g, 14.4 mmol) in CH3CN (30 mL) were
added triethyl orthobenzotate (9.9 mL, 43.2 mmol) and a catalytic
amount of camphorsulfonic acid (334 mg, 1.44 mmol). The mixture
was refluxed for 4 h, and then five drops of Et3N were added to
quench the reaction. CH3CN was evaporated and 30 mL of DMF
was added. The mixture was then cooled to 0 °C and 60% NaH
(1.2 g, 28.8 mmol) was added. The mixture was stirred at rt for
1 h and then cooled to 0 °C. BnBr (2.5 mL, 28.8 mmol) was added
dropwise. After 2 h, 1 M HCl (40 mL) was added to the mixture,
and the suspension was stirred for 1 h. The mixture was then ex-
tracted with CH2Cl2 (3 ꢂ 40 mL), and the combined organic layers
3.2. General procedures
3.2.1. Glycosylation employing thioglycoside
To a solution of glycosyl donor (1.2 equiv) and glycosyl acceptor
(1.0 equiv) in anhyd CH2Cl2 with argon protection was added 4 Å

1526
C. Zong et al. / Carbohydrate Research 345 (2010) 1522–1532
were dried (Na2SO4) and concentrated. Column chromatography
(silica gel, 1:5 EtOAc–petroleum ether) of the residue gave mono-
NMR (pyridine-d5, 150 MHz): d 170.6, 166.7, 160.8, 150.5, 139.0,
136.2, 134.27, 130.5, 129.5, 129.0, 128.3, 124.1, 95.3, 73.9, 73.3,
72.5, 70.9, 68.4, 21.0, 16.5; ESIMS (positive ion): m/z 423.1
[MꢁCNCCl3+Na]+ (Calcd 423.1).
fucoside 10 as a white foam (4.2 g, 71% for three steps): ½a D20
ꢃ
ꢁ293 (
a
) and ꢁ50.9 (b) (c 0.6, CHCl3), Rf 0.45 (
a) and 0.43 (b)
(3:1 EtOAc–petroleum ether).
a
-Isomer: 1H NMR (CDCl3, 600 MHz): d 7.0–8.0 (m, 8H, PhH),
3.3.4. Octyl 3-O-acetyl-4-O-benzoyl-2-O-benzyl-a-L-fucopyrano-
5.61 (d, 1H, J 5.04 Hz, H-4), 5.49 (d, 1H, J 3.3 Hz, H-1), 4.78, 4.56
(2d, 2 ꢂ 1H, J 11.0 Hz, PhCH2), 4.51 (m, 1H, H-5), 4.11(dd, 1H, J
3.2, 7.8 Hz, H-3), 2.59 (m, 2H, CH2CH3), 1.32 (t, 3H, CH3CH2), 1.19
(d, 3H, J 6.4 Hz, H-6); 13C NMR (CDCl3, 150 MHz): d 166.6, 137.4,
133.3, 130.0, 129.9, 128.6, 128.5, 128.4, 128.4, 128.2, 127.9, 82.9,
75.9, 73.3, 71.9, 69.3, 65.4, 29.8, 24.1, 16.3, 15.0. b-Isomer: 1H
NMR (CDCl3, 600 MHz): d 7.0–8.0 (m, 8H, PhH), 5.42 (d, 1H, J
3.3 Hz, H-4), 4.98, 4.70 (dd, 2H, J 11.0 Hz, PhCH2), 4.50 (d, 1H, J
9.9 Hz, H-1), 3.91 (dd, J 3.3, 8.8 Hz, 1H, H-3), 3.80 (m, 1H, H-5),
2.82 (m, 2H, CH2CH3), 1.37 (t, 3H, CH3CH2), 1.25 (d, 3H, J 5.5 Hz,
H-6); 13C NMR (CDCl3, 150 Hz): d 167.1, 138.3, 133.6, 130.3,
129.9, 128.8, 128.7, 128.4, 85.2, 79.0, 75.8, 74.4, 73.8, 73.7, 25.3,
17.0, 15.3. The products were used directly in Section 3.3.2.
side (13)
Glycosylation of the
a-L-fucoside 11 (853 mg, 1.9 mmol) with
n-octanol (395 lL, 2.50 mmol) as described in Section 3.2.1 gave
the monosaccharide 13 as a white foam (984 mg, 94%): ½a D20
ꢃ
ꢁ117.2 (c 0.6, CHCl3); Rf 0.60 (5:1 EtOAc–petroleum ether). 1H
NMR (CDCl3, 600 MHz): d 7.0–8.0 (m, 8H, PhH), 5.48 (d, 1H, J
3.2 Hz, H-4), 5.37 (dd, 1H, J 3.2, 10.5 Hz, H-3), 4.82 (d, 1H, J
3.7 Hz, H-1), 4.69, 4.49 (2d, 2 ꢂ 1H, J 11 Hz, PhCH2), 4.18 (m, 1H,
H-5), 3.89 (dd, 1H, J 3.7, 10.5 Hz, H-2), 3.61 and 3.38 (m, 2H,
CH3(CH2)6CH2O), 1.88 (s, 3H, CH3CO), 1.59 (m, 2H,
CH3(CH2)5CH2CH2O), 1.31 (m, 2H, CH3(CH2)4CH2(CH2)2O), 1.23
(m, 8H, CH3(CH2)4(CH2)3O), 1.09 (d, 3H, J 6.5 Hz, H-6), 0.83 (t,
3H, J 7.1 Hz, CH3(CH2)7O); 13C NMR (CDCl3, 150 MHz): d 170.3,
166.2, 138.3, 133.3, 129.9, 129.8, 128,6, 128.4, 127.9, 97.6, 77.3,
76.9, 73.6, 72.9, 72.3, 70.5, 68.7, 64.6, 31.9, 29.6, 29.5, 29.3, 22.7,
21.0, 16.1, 14.2; HRESIMS (positive ion): m/z 535.2660 [M+Na]+
(Calcd 535.2672).
3.3.2. Ethyl 3-O-acetyl-4-O-benzoyl-2-O-benzyl-1-thio-L-
fucopyranoside (11)
To a solution of monofucoside 10 (4.21 g, 10.5 mmol) in pyri-
dine (40 mL) were added Ac2O (2 mL, 21.0 mmol) and DMAP
(128.1 mg, 1.05 mmol). The mixture was stirred at rt for 1 h and
then MeOH (2 mL) was added. The solution was concentrated
and column chromatography of the residue gave monofucoside
3.4. Octyl 4-O-benzoyl-2-O-benzyl-a-L-fucopyranoside (14)
Deacetylation of 13 as described in Section 3.2.3 gave the
11 as a white foam (3.9 g, 84%), ½a D20
ꢃ
ꢁ193.7 (
a
) and ꢁ139.8 (b)
monosaccharide 14 as a white foam (627 mg, 76%), ½a D20
ꢁ61.2
ꢃ
(c 0.6, CHCl3), Rf 0.41 (
a
) and 0.40 (b) (5:1 EtOAc–petroleum ether).
(c 0.4, CHCl3); Rf 0.37 (5:1 EtOAc–petroleum ether,); 1H NMR
(CDCl3, 600 MHz): d 7.0–8.0 (m, 8H, PhH), 5.49 (d, 1H, J 2.8 Hz,
H-4), 4.91 (d, 1H, J 3.3 Hz, H-1), 4.79, 4.59 (2d, 2 ꢂ 1H, J 11 Hz,
PhCH2), 4.29 (dd, 1H, J 3.8, 9.9 Hz, H-3), 4.15 (m, 1H, H-5), 3.82
(dd, 1H, J 3.3, 9.9 Hz, H-2), 3.66 and 3.39 (m, 2H, CH3(CH2)6CH2O),
a
-Isomer: 1H NMR (CDCl3, 600 MHz): d 7.0–8.0 (m, 8H, 2PhH),
5.55 (d, 1H, J 5.5 Hz, H-4), 5.53 (d, J 3.2 Hz, 1H, H-1), 5.28 (dd,
1H, J 3.2, 10.5 Hz, H-3), 4.85, 4.55 (2d, 2 ꢂ 1H, J 11 Hz, PhCH2),
4.60 (m, 1H, H-5), 4.20 (dd, 1H, J 5.5, 10.5 Hz, H-2), 2.60 (m, 2H,
CH2CH3), 1.93 (s, 3H, CH3CO), 1.32 (t, 3H, CH3CH2), 1.18 (d, 3H, J
6.4 Hz, H-6); 13C NMR (CDCl3, 150 MHz): d 170.2, 166.1, 137.8,
133.4, 129.9, 129.8, 128.6, 128.4, 127.9, 83.5, 77.3, 76.9, 73.0,
72.4, 72.0, 71.1, 65.0, 24.0, 20.9, 16.2, 14.9. b-Isomer: 1H NMR
(CDCl3, 600 MHz): d 7.0–8.0 (m, 8H, 2PhH), 5.45 (d, 1H, J 3.2 Hz,
H-4), 5.06 (dd, 1H, J 3.2, 9.6 Hz, H-3), 4.79, 4.59 (2d, 2 ꢂ 1H, J
11 Hz, PhCH2), 4.53 (d, 1H, J 9.6 Hz, H-1), 3.84 (m, 1H, H-5), 3.69
(t, 1H, H-2), 2.77 (m, 2H, CH2CH3), 1.85 (s, 3H, CH3CO), 1.31 (t,
1.63
(m,
2H,
CH3(CH2)5CH2CH2O),
1.35
(m,
2H,
CH3(CH2)4CH2(CH2)2O), 1.30 (m, 8H, CH3(CH2)4(CH2)3O), 1.17 (d,
3H, J 6.0 Hz, H-6), 0.89 (t, 3H, J 7.1 Hz, CH3(CH2)7O); 13C NMR
(CDCl3, 150 MHz): d 167.0, 138.2, 133.6, 133.5, 133.3, 130.1,
130.0, 129.9, 128.7, 128.6, 128.5, 128.3, 128.2, 96.9, 73.4, 77.2,
76.9, 74.5, 73.8, 72.7, 68.5, 68.3, 65.0, 32.0, 29.7, 29.5, 29.4,
26.3, 22.8, 16.5, 14.2; HRESIMS (positive ion): m/z 493.2573
[M+Na]+ (Calcd 493.2566).
3H, CH3CH2), 1.20 (d, 3H,
J
6.4 Hz, H-6); 13C NMR (CDCl3,
150 MHz): d 170.3, 166.1, 138.0 133.4, 130.0, 129.9, 129.6, 128.6,
128.4, 128.0, 127.9, 85.3, 77.3, 76.9, 76.3, 75.6, 74.8, 73.2, 71.6,
25.2, 20.8, 16.7, 15.1; ESIMS (positive ion): m/z 467.3 [M+Na]+
(Calcd 467.2). The products were used directly in Section 3.3.3.
3.5. Octyl 3-O-acetyl-4-O-benzoyl-2-O-benzyl-
a-L-fucopyranosyl-
(1?3)-4-O-benzoyl-2-O-benzyl- -fucopyranoside (15)
a-L
Glycosylation of monofucoside 14 (627 mg, 1.3 mmol) with b-
configured 11 (801 mg, 1.47 mmol) as described in Section 3.2.1
3.3.3. 3-O-Acetyl-4-O-benzoyl-2-O-benzyl-
L
-fucopyranosyl
gave disaccharide 15 as a white foam (1.04 g, 87%): ½a D20
ꢁ209.4
ꢃ
trichloroacetimidate (12)
(c 0.4, CHCl3); Rf 0.40 (5:1 EtOAc–petroleum ether); 1H NMR
To a solution of 11 (2.0 g, 4.5 mmol) in 9:1 acetone–water
(20 mL) was added NBS (2.4 g, 13.5 mmol). The mixture was stirred
at rt for 2 h. The acetone was evaporated, the mixture was ex-
tracted with CH2Cl2 (3 ꢂ 40 mL), and the combined organic layers
were dried (Na2SO4) and concentrated. The residue was purified
by flash chromatography (3:1 petroleum ether–EtOAc) to give
the hemiacetal as white foam. A mixture of the hemiacetal with tri-
chloroacetonitrile (4 mL, 39.5 mmol) and DBU (298 mL, 2.0 mL) in
anhyd CH2Cl2 (30 mL) was stirred at rt with argon protection for
3 h and then concentrated. The residue was purified by flash chro-
matography (silica gel, deactivated with Et3N, 5:1 petroleum
ether–EtOAc) to give the trichloroacetimidate 12 as a yellow foam
(2.0 g, 93%): Rf 0.37 (3:1 EtOAc–petroleum ether); 1H NMR (pyri-
dine-d5, 600 MHz): d 10.18 (s, 1H, NH), 7.22–8.88 (m, 9H, 2PhH,
H-1), 6.06 (s, 1H, H-4), 5.98 (dd, 1H, J 1.9, 6.3 Hz, H-3), 4.90 (dd,
2H, J 11.0 Hz, PhCH2), 4.75 (m, 1H, H-5), 4.66 (dd, 1H, J 1.9,
6.3 Hz, H-2), 1.97 (s, 3H, CH3CO), 1.28(d, 3H, J 5.4 Hz, H-6); 13C
(CDCl3, 600 MHz): d 7.0–8.0 (m, 20H, PhH), 5.65 (d, 1H, J
3.3 Hz, H-4), 5.43 (dd, 1H, J 3.2, 10.5 Hz, H-3I), 5.35 (d, 1H, J
3.8 Hz, H-1I), 5.32 (d, 1H, J 2.3 Hz, H-4I), 4.95 (d, 1H, J 3.3 Hz,
H-1), 4.76 (dd, 2H, PhCH2), 4.47, 4.30 (2d, 2 ꢂ 1H, J 11 Hz,
PhCH2), 4.46 (m, 1H, H-5I), 4.37 (dd, 1H, J 3.2, 10.1 Hz, H-3),
4.15 (m, 1H, H-5), 4.03 (dd, 1H, J 3.8, 10.4 Hz, H-2), 3.90 (dd,
1H,
J 3.8, 10.4 Hz, H-2I), 3.50, 3.70 (m, 2H, J 6.6, 9.4 Hz,
CH3(CH2)6CH2O), 1.79 (s, 3H, COCH3), 1.66 (m, 2H,
CH3(CH2)5CH2CH2O), 1.40 (m, 2H, CH3(CH2)4CH2(CH2)2O), 1.29
(m, 8H, CH3(CH2)4(CH2)3O), 1.15 (d, 3H, J 6.6 Hz, H-6), 0.97 (d,
3H, J 6.6 Hz, H-6I), 0.87 (t, 3H, J 7.1 Hz, CH3(CH2)7O); 13C NMR
(CDCl3, 150 MHz): d 170.2, 166.6, 166.2, 138.3, 138.2, 133.1,
130.0, 129.9, 129.8, 128.6, 128.5, 128.3, 128.1, 127.9, 127.7,
127.4, 97.5, 92.9, 77.3, 76.9, 74.7, 73.1, 72.7, 72.4, 72.3, 70.5,
70.3, 69.9, 68.6, 64.9, 64.7, 31.9, 29.8, 29.6, 29.5, 29.4, 26.3,
22.8, 20.9, 16.4, 16.0, 14.2; HRESIMS (positive ion): m/z
875.3970 [M+Na]+ (Calcd 875.3982).

C. Zong et al. / Carbohydrate Research 345 (2010) 1522–1532
1527
3.6. Octyl 4-O-benzoyl-2-O-benzyl-
a
-
L
-fucopyranosyl-(1?3)-4-
2 ꢂ H-6); 13C NMR (CDCl3, 150 MHz): d 170.0, 166.6, 166.4, 166.2,
138.2, 138.0, 137.9, 137.7, 133.6, 133.2, 133.1, 132.9, 130.0, 129.9,
129.8, 128.9, 128.8, 128.7, 128.6, 128.5, 128.4, 128.3, 128.1, 128.0,
127.6, 127.5, 127.2, 97.7, 93.4, 92.7, 92.6, 78.1, 77.3, 77.0, 76.9,
73.1, 72.7, 72.3, 72.1, 70.9, 70.7, 70.3, 70.2, 70.1, 69.6, 68.5, 65.5,
65.1, 64.8, 64.3, 31.9, 29.8, 29.6, 29.5, 29.4, 26.3, 22.8, 20.9, 20.8,
16.6, 16.4, 16.3, 16.2, 16.0, 15.6, 14.2; HRMALDIMS (positive ion):
m/z 1555.6599 [M+Na]+ (Calcd 1555.6608).
O-benzoyl-2-O-benzyl- -fucopyranoside (16)
a
-L
Deacetylation of 15 as described in Section 3.2.3 gave disaccha-
ride acceptor 16 as a white foam (759.3 mg, 80.5%): ½a D20
ꢁ177.1 (c
ꢃ
0.4, CHCl3); Rf 0.20 (5:1 EtOAc–petroleum ether); 1H NMR (CDCl3,
600 MHz): d 7.0–8.0 (m, 20H, PhH), 5.68 (d, 1H, J 2.7 Hz, H-4),
5.44 (d, 1H, J 2.7 Hz, H-1I), 5.23 (d, 1H, J 2.2 Hz, H-4I), 4.92(d, 1H,
J 3.3 Hz, H-1), 4.83, 4.63 (2d, 2 ꢂ 1H, J 11 Hz, PhCH2), 4.56, 4.35
(2d, 2 ꢂ 1H, J 11 Hz, PhCH2), 4.43 (d, 1H, J 2.8 Hz, H-3), 4.40 (m,
1H, H-5I), 4.18 (m, 1H, H-5), 4.17(m, 1H, H-3I), 4.01 (dd, 1H, J 3.3,
9.8 Hz, H-2), 3.78 (dd, 1H, J 3.3, 9.9 Hz, H-2I), 3.49 and 3.69 (m,
2H, CH3(CH2)6CH2O), 1.65 (m, 2H, CH3(CH2)5CH2CH2O), 1.40 (m,
2H, CH3(CH2)4CH2(CH2)2O), 1.29 (m, 8H, CH3(CH2)4(CH2)3O), 1.15
(d, 3H, J 6.5 Hz, H-6), 1.05 (d, 3H, J 6.6 Hz, H-6I), 0.87 (t, 3H, J
7.1 Hz, CH3(CH2)7O); 13C NMR (CDCl3, 150 MHz): d 166.6, 166.2,
138.4, 137.8, 133.3, 133.1, 130.1, 130.0, 129.9, 129.7, 128.6,
128.5, 128.4, 128.1, 127.9, 127.7, 97.5, 92.0, 77.3, 76.9, 75.6, 74.6,
73.6, 73.0, 71.8, 70.2, 70.1, 68.6, 68.0, 65.2, 65.0, 31.9, 29.7, 29.5,
29.4, 26.3, 22.8, 16.4, 16.2, 14.2; HRESIMS (positive ion): m/z
833.3870 [M+Na]+ (Calcd 833.3877).
3.9. Octyl 3-O-acetyl-4-O-benzoyl-
O-benzoyl- -fucopyranosyl-(1?3)-4-O-benzoyl-
fucopyranosyl-(1?3)-4-O-benzoyl- -fucopyranoside (19)
a-L-fucopyranosyl-(1?3)-4-
a-L
a-L-
a
-L
Debenzylation of 18 (40 mg, 0.027 mmol) as described in Sec-
tion 3.2.4 gave 19 as a white foam (31.9 mg, 81%): ½a D20
ꢁ277.1 (c
ꢃ
0.33, MeOH); Rf 0.30 (2:1 PhCH3–EtOAc); 1H NMR (CDCl3,
600 M Hz): d 7.10–8.10 (m, 20H, PhH), 5.53 (d, 1H, J 2.8 Hz, H-4),
5.40 (d, 1H, J 2.8 Hz, H-4), 5.38 (d, 1H, J 1.9 Hz, H-4), 5.36 (d, 1H,
J 3.2 Hz, H-4), 5.19 (d, 1H, J 3.7 Hz, H-1II), 5.03 (d, 1H, J 4.1 Hz, H-
1III), 5.02 (dd, 1H, J 3.8, 10.4 Hz, H-3IV), 5.01 (d, 1H, J 3.7 Hz, H-
1IV), 4.97 (d, 1H, J 3.7 Hz, H-1I), 4.47–4.18 (m, 4H, 4 ꢂ H-5), 4.05–
3.82 (m, 8H, 4 ꢂ H-3, 4 ꢂ H-2), 3.78–3.52 (m, 2H, CH3(CH2)6CH2O),
1.93 (s, 3H, CH3CO), 1.25–1.68 (m, 12H, CH3(CH2)6CH2O), 0.96 (t,
3H, J 7.4 Hz, CH3(CH2)7O), 1.17, 1.07, 0.98, 0.85 (4 d, each 3H,
4 ꢂ H-6); 13C NMR (CDCl3, 150 MHz) d 171.0, 167.9, 167.6, 166.3,
134.1, 133.9, 133.5, 131.2, 130.3, 130.1, 129.7, 129.6, 129.2,
129.0, 128.9, 128.8, 100.8, 99.6, 99.0, 79.7, 77.6, 77.5, 77.4, 77.3,
77.1, 73.2, 73.0, 72.9, 72.4, 72.1, 71.6, 69.0, 68.6, 68.2, 68.0, 67.3,
66.3, 66.0, 65.9, 65.6, 65.3, 51.1, 32.2, 32.1, 30.0, 29.8, 29.7, 29.6,
28.0, 26.6, 23.0, 21.2, 19.5, 16.5, 16.1, 15.9, 14.4; HRESIMS (positive
ion): m/z 1195.4756 [M+Na]+ (Calcd 1195.4726).
3.7. Ethyl 3-O-acetyl-4-O-benzoyl-2-O-benzyl-
a-L-fucopyranosyl-
(1?3)-4-O-benzoyl-2-O-benzyl- -fucopyranoside (17)
a
-L
Glycosylation of b-configured monofucoside 10 (50 mg,
0.12 mmol) with trichloroacetimidate 12 (81.7 mg, 0.15 mmol) as
described in Section 3.2.2 gave disaccharide 17 as a white foam
(71.8 mg, 73.4%): ½a D20
ꢁ191.9 (c 0.4, CHCl3); Rf 0.40 (5:1 EtOAc–
ꢃ
petroleum ether); 1H NMR (CDCl3, 600 MHz): d 7.0–8.0 (m, 20H,
PhH), 5.68 (d, 1H, J 3.2 Hz, H-4), 5.42 (dd, 1H, J 3.3, 11.5 Hz, H-
3I), 5.39 (d, 1H, J 3.3 Hz, H-1I), 5.22 (d, 1H, J 2.2 Hz, H-4I), 5.10,
4.73 (2d, 2 ꢂ 1H, J 11 Hz, PhCH2), 4.59(d, 1H, J 9.9 Hz, H-1), 4.32,
4.48 (2d, 2 ꢂ 1H, J 11 Hz, PhCH2), 4.26 (m, 1H, H-5), 4.03 (dd, 1H,
J 3.3, 9.4 Hz, H-3), 3.90 (dd, 1H, J 2.8, 10.4 Hz, H-2I), 3.84(m, 1H,
H-2), 3.82(m, 1H, H-5I), 2.86(m, 2H, CH3CH2S), 1.81 (s, 3H, CH3CO),
3.10. Octyl 2-O-benzyl-
-fucopyranosyl-(1?3)-2-O-benzyl-
O-benzyl- -fucopyranoside (21)
a
-
L
-fucopyranosyl-(1?3)-2-O-benzyl-
a-
L
a-L
-fucopyranosyl-(1?3)-2-
a
-L
1.40 (t, 3H, CH3CH2S), 0.88 (m, 3H, H-6), 0.82(d, 3H, J 6.6, H-6I); 13
C
Compound 18 (28.5 mg, 0.0186 mmol) was dissolved in
1:1 MeOH–CH2Cl2 (20 mL), and the pH was adjusted to 11 by addi-
tion of MeONa. The mixture was stirred for 3 h at rt, then neutral-
ized with Dowex 50-X8 resin (H+ form), filtered, and concentrated.
The crude product was loaded on a column of LH-20 to afford 21 as
NMR (CDCl3, 150 MHz): d 170.2, 166.6, 166.1, 138.0, 137.9, 133.3,
133.2, 130.1, 130.0, 129.8, 129.5, 128.7, 128.5, 128.2, 128.1,
127.9, 127.5, 92.7, 85.4, 76.4, 75.3, 73.4, 72.4, 72.3, 72.2, 70.2,
68.6, 64.7, 32.0, 29.8, 29.5, 24.9, 22.8, 20.9, 17.0, 15.8, 15.2, 14.2;
HRESIMS (positive ion): m/z 807.2802 [M+Na]+ (Calcd 807.2815).
a white foam (20 mg, 100%): ½a D20
ꢁ16.3 (c 0.2, CHCl3); Rf 0.30
ꢃ
(DCM–MeOH, 30:1); 1H NMR (CDCl3, 600 MHz): d 7.30 (m, 20H,
4 ꢂ Ph), 4.83 (m, 1H, J 2.76 Hz, H-4), 4.77 (d, 1H, J 3.30 Hz, H-1),
4.75–4.56 (8H, PhCH2), 4.08 (m, 1H, H-5), 4.03 (m, 1H, H-5), 4.01
(dd, 1H, J 3.24, 9.84 Hz, H-3), 3.93 (m, 5H, 2H-5, 3 ꢂ H-3), 3.80
(m, 3H, 3H-2), 3.74 (dd, 1H, J 3.30, 9.90 Hz, H-2), 3.67 (m, 2H,
2 ꢂ H-4), 3.62 (m, 1H, one proton of CH3(CH2)6CH2O), 3.45 (m,
3H, 3 ꢂ H-4), 3.42 (m, 1H, one proton of CH3(CH2)6CH2O), 1.60
3.8. Octyl 3-O-acetyl-4-O-benzoyl-2-O-benzyl-
a
-
a
a
a
L
-
fucopyranosyl-(1?3)-4-O-benzoyl-2-O-benzyl-
fucopyranosyl-(1?3)-4-O-benzoyl-2-O-benzyl-
fucopyranosyl-(1?3)-4-O-benzoyl-2-O-benzyl-
fucopyranoside (18)
-
-
-
L-
L-
L
-
Glycosylation of acceptor 16 (128.3 mg, 0.16 mmol) and donor
17 (150.7 mg, 0.19 mmol) as described in Section 3.2.1 gave tetra-
(m,
2H,
CH3(CH2)5CH2CH2O),
1.39–1.18
(m,
10H,
CH3(CH2)5(CH2)2O), 1.14 (m, 12H, 4 ꢂ H-6), 0.88 (t, 3H, J 7.1 Hz,
CH3(CH2)7O); 13C NMR (CDCl3, 150 MHz): d 138.7, 137.7, 137.5,
128.9, 128.7, 128.6, 128.5, 128.4, 128.3, 128.1, 127.8, 127.6, 96.9,
94.2, 94.1, 93.7, 76.5, 75.0, 74.9, 74.7, 74.6, 74.4, 74.3, 72.4, 72.1,
70.1, 68.4, 68.2, 66.2, 65.7, 64.7, 32.0, 31.9, 29.7, 29.5, 29.4, 29.3,
26.2, 22.7, 16.4, 16.1, 16.0, 14.1; HRMALDIMS (positive ion): m/z
[M+Na]+ 1097.5410 (Calcd 1097.5421).
saccharide 18 as a white foam (188 mg, 80.8%): ½a D20
ꢁ265.6 (c
ꢃ
0.4, CHCl3); Rf 0.29 (5:1 EtOAc–petroleum ether); 1H NMR (CDCl3,
600 MHz): d 7.10–8.10 (m, 40H, 8 ꢂ Ph), 5.67 (d, 1H, J 2.7 Hz, H-
4I), 5.47 (d, 1H, J 2.2 Hz, H-4), 5.30 (d, 1H, J 3.3 Hz, H-1II), 5.28 (d,
1H, J 3.8 Hz, H-1III), 5.25 (dd, 1H, J 3.8, 10.4 Hz, H-3IV), 5.17 (d, 1H,
J 2.8 Hz, H-4), 5.10 (d, 1H, J 3.3 Hz, H-1IV), 5.02 (d, 1H, J 2.8 Hz, H-
4IV), 4.88 (d, 1H, J 3.3 Hz, H-1I), 4.86, 4.66 (2d, 2 ꢂ 1H, J 11 Hz,
PhCH2), 4.59–4.37 (m, 5H, H-3I,H-5I, H-3II, and PhCH2), 4.37–4.02
3.11. Octyl 4-O-benzoyl-2-O-benzyl-
O-benzoyl-2-O-benzyl- -fucopyranosyl-(1?3)-4-O-benzoyl-2-
O-benzyl- -fucopyranosyl-(1?3)-4-O-benzoyl-2-O-benzyl-
-fucopyranoside (23)
a-L-fucopyranosyl-(1?3)-4-
(m, 9H, 2 ꢂ PhCH2, H-5II, H-3III, H-5
H-5IV, H-2II), 4.00 (dd, 1H, J
III,
a-L
3.8, 10.4 Hz, H-2II), 3.93 (dd, J 3.3, 10.4 Hz, H-2III), 3.77 (dd, 1H, J
3.3, 10.4 Hz, H-2IV), 3.68 (m, 1H, one proton of CH3(CH2)6CH2O),
3.50 (m, 1H, one proton of CH3(CH2)6CH2O), 1.73 (s, 3H, CH3CO),
a
-L
a-
L
1.65(m,
2H,
CH3(CH2)5CH2CH2O),
1.39–1.26
(m,
10H,
Deacetylation of 18 (337.7 mg, 0.22 mmol) as described for the
preparation of 14 gave tetrasaccharide 23 as a white foam
CH3(CH2)5(CH2)2O), 1.16, 1.02 (d, each 3H, J 6.6 Hz, 2 ꢂ H-6), 0.88
(t, 3H, J 7.1 Hz, CH3(CH2)7O), 0.74, 0.57 (d, each 3H, J 6.1 Hz,

1528
C. Zong et al. / Carbohydrate Research 345 (2010) 1522–1532
(328.5 mg, 86.8%): ½a D20
ꢃ
ꢁ98.5 (c 0.2, CHCl3); Rf 0.21 (5:1 EtOAc–
69.9, 68.8, 67.9, 65.6, 65.3, 65.2, 65.1, 64.9, 64.8, 32.1, 30.0,
29.8, 29.7, 29.6, 26.5, 23.0, 16.7, 16.5, 16.3, 16.2, 16.1, 14.4; HRM-
ALDIMS (positive ion): m/z 2183.9080 [M+Na]+ (Calcd
2193.9078).
petroleum ether); 1H NMR (CDCl3, 600 MHz): d 8.04–6.97 (m,
40H, PhH), 5.67–4.83 (8d, 8H, 4 ꢂ H-1, 4 ꢂ H4), 4.86, 4.66 (2d,
2 ꢂ 1H, J 11 Hz, PhCH2), 4.63–4.23 (m, 6H, PhCH2), 4.42–3.62
(m, 12H, 4H-5, 4H-3, 4H-2), 3.68 (m, 1H, one proton of
CH3(CH2)5CH2O), 3.50 (m, 1H, one proton of CH3(CH2)5CH2O),
1.70–1.24 (m, 12H, CH3(CH2)6CH2O), 1.16, 1.03, 0.71, 0.70 (d, each
3H, 12H, J 6.6 Hz, 4 ꢂ H-6), 0.88 (t, 3H, J 7.1 Hz, CH3(CH2)7O); 13C
NMR (CDCl3, 150 MHz): d 166.5, 166.4, 138.2, 138.1, 137.9, 137.8,
133.2, 133.1, 130.0, 129.9, 129.8, 129.7, 128.5, 128.4, 128.3, 128.2,
128.1, 128.0, 127.9, 127.8, 127.6, 127.5, 97.7, 93.3, 91.6, 77.3,
77.1, 76.9, 75.4, 74.2, 74.1, 73.7, 73.5, 73.1, 72.8, 72.7, 71.5,
70.9, 70.7, 70.3, 70.1, 69.8, 69.7, 68.5, 67.7, 65.4, 65.1, 64.8,
64.6, 31.9, 29.6, 29.5, 29.4, 26.3, 22.7, 16.4, 16.3, 16.0, 15.9,
14.2; HRMALDIMS (positive ion): m/z [M+Na]+ 1513.6492 (Calcd
1513.6480).
3.14. Octyl 4-O-benzoyl-2-O-benzyl-
O-benzoyl-2-O-benzyl- -fucopyranosyl-(1?3)-4-O-benzoyl-2-
O-benzyl- -fucopyranosyl-(1?3)-4-O-benzoyl-2-O-benzyl-
-fucopyranosyl-(1?3)-4-O-benzoyl-2-O-benzyl- -fucopyran-
osyl-(1?3)-4-O-benzoyl-2-O-benzyl- -fucopyranosyl-(1?3)-
4-O-benzoyl-2-O-benzyl- -fucopyranoside (26)
a-L-fucopyranosyl-(1?3)-4-
a-L
a
-L
a-
L
a-L
a
-L
a
-L
Deacetylation of 29 (127.9 mg, 0.053 mmol) as described for
the preparation of 14 gave 26 as a white foam (116.1 mg,
92.4%): ½a 2D0
ꢁ103.8 (c 0.2, CHCl3); Rf 0.25 (3:1 EtOAc–petro-
ꢃ
leum ether,); 1H NMR (CDCl3, 600 MHz): d 8.04–6.95 (m, 60H,
PhH), 5.67–4.80 (14d, 14H, 7 ꢂ H-1, 7 ꢂ H-4), 4.87, 4.67 (2d,
2 ꢂ 1H, J 11 Hz, PhCH2), 4.63–4.20 (m, 12H, PhCH2), 4.43–3.59
(m, 21H, 7H-5, 7H-3, 7H-2), 3.68 (m, 1H, one proton of
CH3(CH2)6CH2O), 3.51 (m, 1H, one proton of CH3(CH2)6CH2O),
1.70–1.24 (m, 12H, CH3(CH2)6CH2O), 1.15, 1.03, 0.72, 0.66,
0.65, 0.61, 0.60 (7d, each 3H, 21H, J 6.6 Hz, 7 ꢂ H-6), 0.88 (t,
3.12. Octyl 4-O-benzoyl-2-O-benzyl-
O-benzoyl-2-O-benzyl- -fucopyranosyl-(1?3)-4-O-benzoyl-2-
O-benzyl- -fucopyranosyl-(1?3)-4-O-benzoyl-2-O-benzyl-
-fucopyranosyl-(1?3)-4-O-benzoyl-2-O-benzyl- -fuco-
pyranoside (24)
a-L-fucopyranosyl-(1?3)-4-
a-L
a-
L
a-
L
a-L
3H,
J d
7.1 Hz, CH3(CH2)7O); 13C NMR (CDCl3, 150 MHz):
Deacetylation of 28 (535.7 mg, 0.29 mmol) as described for the
166.7, 166.6, 138.5, 138.4, 138.3, 138.2, 138.1, 133.5, 133.4,
133.3, 130.4, 130.3, 130.2, 130.1, 130.0, 129.3, 128.8, 128.7,
128.6, 128.5, 128.4, 128.3, 128.2, 128.0, 127.8, 127.7, 97.9,
93.5, 93.3, 93.2, 92.9, 91.8, 77.6, 77.4, 77.2, 75.6, 74.5, 74.4,
73.9, 73.8, 73.4, 72.9, 72.8, 71.8, 71.2, 70.9, 70.7, 70.5, 70.4,
70.1, 69.9, 68.8, 67.9, 65.6, 65.4, 65.2, 65.1, 65.0, 64.9, 32.2,
30.0, 29.8, 29.7, 29.6, 26.5, 23.0, 16.7, 16.5, 16.3, 16.2, 16.1,
14.4; HRMALDIMS (positive ion): m/z [M+Na]+ 2576.0531 (Calcd
2576.0541).
preparation of 14 gave 24 as a white foam (400.6 mg, 77%): ½a D20
ꢃ
ꢁ221.9 (c 0.2, CHCl3); Rf 0.48 (3:1 EtOAc–petroleum ether); 1H
NMR (CDCl3, 600 MHz): d 8.04–6.93 (m, 50H, PhH), 5.67–4.81
(10d, 10H, 5 ꢂ H-1, 5 ꢂ H4), 4.77 (q, 2H, J 11.0 Hz, PhCH2), 4.63–
4.28 (m, 8H, PhCH2), 4.42–3.60 (m, 15H, 5H-5, 5H-3, 5H-2), 3.67
(m, 1H, one proton of CH3(CH2)6CH2O), 3.50 (m, 1H, one proton
of CH3(CH2)6CH2O), 1.70–1.25 (m, 12H, CH3(CH2)6CH2O), 1.15,
1.04, 0.70, 0.66, 0.63 (d, each 3H, 15H, J 6.6 Hz, 5 ꢂ H-6), 0.87 (t,
3H, J 7.1 Hz, CH3(CH2)7O); 13C NMR (CDCl3, 150 MHz): d 166.7,
166.6, 138.8, 138.5, 138.3, 138.2, 138.1, 133.4, 133.2, 130.4,
130.3, 130.2, 130.1, 130.0, 128.7, 128.6, 128.5, 128.4, 128.3,
128.2, 128.1, 128.0, 127.8, 127.7, 97.9, 95.3, 93.4, 93.0, 91.8,
77.6, 77.5, 77.4, 77.3, 77.1, 77.0, 74.4, 74.0, 73.9, 73.8, 73.3, 73.0,
72.9, 71.8, 71.1, 70.9, 70.7, 70.6, 70.4, 70.3, 70.0, 68.8, 68.0, 65.6,
65.3, 65.2, 65.0, 64.9, 32.1, 30.0, 29.8, 29.7, 29.6, 26.5, 23.0, 16.6,
16.5, 16.2, 16.1, 14.4; HRMALDIMS (positive ion): m/z 1853.7828
[M+Na]+ (Calcd 1853.7817).
3.15. Octyl 3-O-acetyl-4-O-benzoyl-2-O-benzyl-
osyl-(1?3)-4-O-benzoyl-2-O-benzyl- -fucopyranosyl-(1?3)-
4-O-benzoyl-2-O-benzyl- -fucopyrano-syl-(1?3)-4-O-benzoyl-
2-O-benzyl- -fucopyranosyl-(1?3)-4-O-benzoyl-2-O-benzyl-
a-L-fucopyran-
a
-L
a-L
a-L
a-L
-fucopyranoside (27)
Glycosylation of tetrasaccharide 23 (268 mg, 0.18 mmol) with
12 (101.8 mg, 0.22 mmol) as described in Section 3.2.2 gave
pentasaccharide 27 as white foam (310.6 mg, 92%):
a
½ ꢃ
a 2D0
3.13. Octyl 4-O-benzoyl-2-O-benzyl-
O-benzoyl-2-O-benzyl- -fucopyranosyl-(1?3)-4-O-benzoyl-2-
O-benzyl- -fucopyranosyl-(1?3)-4-O-benzoyl-2-O-benzyl-
-fucopyranosyl-(1?3)-4-O-benzoyl-2-O-benzyl- -fuco-
-fucopyranoside
a-L
-fucopyranosyl-(1?3)-4-
ꢁ242.0 (c 0.5, CHCl3); Rf 0.58 (3:1 EtOAc–petroleum ether); 1H
NMR (CDCl3, 600 MHz): d 7.10–8.10 (m, 50H, PhH), 5.59 (d, 1H,
J 2.8 Hz, H-4), 5.38 (d, 1H, J 2.4 Hz, H-4), 5.28 (d, 1H, J 3.2 Hz,
H-1), 5.15(dd, 1H, J 3.8, 10.4 Hz, H-3V), 5.09 (d, 1H, J 2.8 Hz, H-
4), 5.07 (m, 2H, 2 ꢂ H-1), 5.03(d, 1H, J 2.8 Hz, H-4), 5.00 (d, 1H,
J 3.3 Hz, H-1V), 4.92 (d, 1H, J 2.8 Hz, H-4V), 4.81 (d, 1H, J 3.8 Hz,
H-1), 4.70 (dd, 2H, J 11.0 Hz, PhCH2), 4.56–4.10 (m, 12H, 3 ꢂ H-
3, 1 ꢂ H-5, 4 ꢂ PhCH2), 4.05 (m, 4H, 3 ꢂ H-5, 1 ꢂ H-3), 3.96 (m,
3H, 2 ꢂ H-2, 1 ꢂ H-5), 3.82 (m, 2H, 2 ꢂ H-2), 3.68 (dd, 1H, J 3.3,
10.4 Hz, H-2V), 3.68 (m, 1H, one proton of CH3(CH2)6CH2O), 3.43
(m, 1H, one proton of CH3(CH2)6CH2O), 1.65 (s, 3H, CH3CO),
a-L
a-
L
a-
L
a-L
pyranosyl-(1?3)-4-O-benzoyl-2-O-benzyl-a-L
(25)
Deacetylation of 28 (312.7 mg, 0.14 mmol) as described for
the preparation of 14 gave tetrasaccharide 25 as a white foam
(287.9 mg, 94%): ½a D20
ꢁ7.47 (c 0.15, CHCl3); Rf 0.26 (3:1 EtOAc–
ꢃ
petroleum ether); 1H NMR (CDCl3, 600 MHz): d 8.03–6.95 (m,
60H, PhH), 5.67–4.80 (12d, 12H, 6 ꢂ H-1, 6 ꢂ H4), 4.77 (q, 2H,
PhCH2), 4.63–4.20 (m, 10H, 5 ꢂ PhCH2), 4.43–3.59 (m, 18H, 6H-
5, 6H-3, 6H-2), 3.68 (m, 1H, one proton of CH3(CH2)6CH2O),
3.51 (m, 1H, one proton of CH3(CH2)6CH2O), 1.70–1.24 (m, 14H,
CH3(CH2)6CH2O), 1.15, 1.03, 0.72, 0.65, 0.64, 0.60 (d, each 3H,
15H, J 6.6 Hz, 5 ꢂ H-6), 0.88 (t, 3H, J 7.1 Hz, CH3(CH2)7O); 13C
1.60(m,
2H,
CH3(CH2)5CH2CH2O),
1.39–1.18
(m,
10H,
CH3(CH2)5(CH2)2O), 1.08, 0.97, 0.63, 0.60, 0.47 (5d, each 3H,
15H, J 6.6 Hz, 5 ꢂ H-6), 0.81 (t, 3H, J 7.1 Hz, CH3(CH2)7O); 13C
NMR (CDCl3, 150 MHz)
d 170.0, 166.5, 166.4, 166.3, 166.2,
138.3, 138.2, 137.9, 137.8, 133.3, 133.1, 130.1, 130.0, 129.9,
129.8, 129.7, 128.5, 128.4, 128.3, 128.2, 128.0, 127.6, 127.5,
127.4, 127.2, 97.7, 93.2, 92.6, 77.3, 77.2, 77.1, 76.9, 76.8, 74.0,
73.8, 73.1, 72.7, 72.6, 72.3, 72.1, 70.9, 70.7, 70.4, 70.2, 70.1,
69.6, 68.5, 65.3, 65.1, 65.0, 64.7, 64.2, 32.0, 31.9, 29.8, 29.7,
29.6, 29.5, 29.4, 26.3, 22.8, 22.7, 20.8, 16.4, 16.3, 16.0, 15.9,
15.6, 14.2; HRMALDIMS (positive ion): m/z 1895.7909 [M+Na]+
(Calcd 1895.7947).
NMR (CDCl3, 150 MHz)
d 166.8, 166.7, 166.6, 138.5, 138.3,
138.2, 138.1, 133.5, 133.4, 133.3, 133.2, 130.4, 130.3, 130.2,
130.1, 130.0, 128.8, 128.7, 128.6, 128.5, 128.4, 128.3, 128.2,
128.1, 128.0, 127.8, 127.7, 97.9, 93.5, 93.3, 93.2, 93.0, 91.8,
77.6, 77.5, 77.4, 77.3, 77.2, 77.0, 75.7, 74.4, 74.2, 74.0, 73.8,
73.3, 73.0, 72.9, 71.8, 71.1, 70.9, 70.7, 70.5, 70.4, 70.3, 70.1,

C. Zong et al. / Carbohydrate Research 345 (2010) 1522–1532
1529
3.16. Octyl 3-O-acetyl-4-O-benzoyl-2-O-benzyl-
osyl-(1?3)-4-O-benzoyl-2-O-benzyl- -fucopyranosyl-(1?3)-4-
O-benzoyl-2-O-benzyl- -fucopyrano-syl-(1?3)-4-O-benzoyl-
2-O-benzyl- -fucopyranosyl-(1?3)-4-O-benzoyl-2-O-benzyl-
-fucopyranosyl-(1?3)-4-O-benzoyl-2-O-benzyl-
fucopyranoside (28)
a
-
L
-fucopyran-
(c 0.5, CHCl3); Rf 0.32 (3:1 EtOAc–petroleum ether); 1H NMR
(CDCl3, 600 MHz): d 8.04–6.97 (m, 80H, PhH), 5.67–4.87 (16d,
16H, 8 ꢂ H-1, 8 ꢂ H-4), 5.21 (dd, 1H, J 3.8, 10.4 Hz, H-3), 4.77,
4.57 (2d, 2 ꢂ 1H, J 11.0 Hz, PhCH2), 4.63–4.06 (m, 12H, PhCH2),
4.42–3.72 (m, 23H, 8H-5, 7H-3, 8H-2), 3.68 (m, 1H, one proton of
CH3(CH2)6CH2O), 3.51 (m, 1H, one proton of CH3(CH2)6CH2O),
1.71 (s, 3H, CH3CO), 1.67–1.20 (m, 12H, CH3(CH2)6CH2O), 1.15,
1.03, 0.72, 0.65, 0.64, 0.62, 0.61, 0.53 (8d, each 3H, 24H, J 6.6 Hz,
8 ꢂ H-6), 0.88 (t, 3H, J 7.1 Hz, CH3(CH2)7O); 13C NMR (CDCl3,
150 MHz): d 170.2, 166.8, 166.6, 166.4, 138.5, 138.4, 138.2, 138.1,
134.9, 133.5, 133.4, 133.3, 133.1, 130.5, 130.4, 130.3, 130.2,
130.1, 130.0, 129.4, 128.8, 128.7, 128.6, 128.5, 128.4, 128.3,
127.8, 127.7, 127.4, 125.6, 97.9, 93.5, 93.4, 93.3, 93.2, 93.1, 92.8,
92.7, 77.6, 77.4, 77.2, 74.4, 74.0, 73.9, 73.8, 73.7, 73.4, 73.3, 73.0,
72.9, 72.8, 72.6, 72.3, 71.1, 70.9, 70.7, 70.6, 70.4, 70.3, 69.9, 68.8,
65.6, 65.4, 65.2, 65.1, 65.0, 64.8, 64.4, 32.2, 30.0, 29.8, 29.7, 29.6,
26.5, 23.0, 21.8, 21.1, 16.7, 16.5, 16.3, 16.2, 15.8, 14.5, 14.4;
HRMALDIMS (positive ion): m/z 2916.1842 [M+Na]+ (Calcd
2916.1894).
a-L
a
-L
a
-L
a-
L
a-L-
Glycosylation of pentasaccharide 24 (400 mg, 0.22 mmol) with
12 (143.8 mg, 0.26 mmol) as described in Section 3.2.2 gave hexa-
saccharide 28 as a white foam (392 mg, 88%): ½a D20
ꢁ311.4 (c 0.5,
ꢃ
CHCl3); Rf 0.53 (3:1 EtOAc–petroleum ether); 1H NMR (CDCl3,
600 MHz): d 8.04–7.00 (m, 60H, PhH), 5.66–4.87 (12d, 12H,
6 ꢂ H-1, 6 ꢂ H4), 5.21 (dd, 1H, J 3.8, 10.4 Hz, H-3), 4.76 (dd, 2H, J
11 Hz, 1 ꢂ PhCH2), 4.64–4.24 (m, 8H, PhCH2), 4.42–3.66 (m, 18H,
6H-5, 6H-3, 6H-2), 3.66 (m, 1H, one proton of CH3(CH2)6CH2O),
3.51 (m, 1H, one proton of CH3(CH2)6CH2O), 1.71 (s, 3H, CH3CO),
1.67–1.21 (m, 14H, CH3(CH2)6CH2O), 1.15, 1.03, 0.72, 0.64, 0.63,
0.53 (d, each 3H, J 6.6 Hz, 18H, 6 ꢂ H-6), 0.88 (t, 3H, J 7.1 Hz,
CH3(CH2)7O); 13C NMR (CDCl3, 150 MHz): d 170.2, 166.8, 166.6,
166.4, 138.5, 138.3, 138.2, 138.1, 133.4, 133.3, 133.1, 130.4,
130.3, 130.2, 130.1, 130.0, 128.8, 128.7, 128.6, 128.5, 128.4,
128.2, 127.8, 127.7, 127.4, 97.9, 93.5, 93.3, 92.8, 77.6, 77.5, 77.4,
76.5, 74.4, 74.0, 73.9, 73.4, 73.3, 72.9, 72.8, 72.3, 71.1, 70.9, 70.8,
70.7, 70.6, 70.4, 68.8, 65.6, 65.4, 65.2, 64.9, 64.4, 32.1, 30.0, 29.9,
29.7, 29.6, 26.5, 23.0, 16.7, 16.5, 16.3, 16.2, 16.1, 15.8, 14.4; HRM-
ALDIMS (positive ion): m/z 2235.9220 [M+Na]+ (Calcd 2235.9209).
3.19. Octyl 3-O-acetyl-4-O-benzoyl-
O-benzoyl- -fucopyranosyl-(1?3)-4-O-benzoyl-
fucopyranosyl-(1?3)-4-O-benzoyl- -fucopyranosyl-(1?3)-4-
O-benzoyl– -fucopyranoside (31)
a-L-fucopyranosyl-(1?3)-4-
a-L
a-L-
a
-L
a-L
Catalytic hydrogenolysis of compound 28 (20 mg, 0.0106 mmol)
as described in Section 3.2.4 gave 31 as a white foam (12 mg, 80%):
3.17. Octyl 3-O-acetyl-4-O-benzoyl-2-O-benzyl-
syl-(1?3)-4-O-benzoyl-2-O-benzyl- -fucopyranosyl-(1?3)-4-
O-benzoyl-2-O-benzyl- -fucopyrano-syl-(1?3)-4-O-benzoyl-
2-O-benzyl- -fucopyranosyl-(1?3)-4-O-benzoyl-2-O-benzyl-
-fucopyranosyl-(1?3)-4-O-benzoyl-2-O-benzyl- -fucopyra-
nosyl-(1?3)-4-O-benzoyl-2-O-benzyl- -fucopyranoside (29)
a-L-fucopyrano-
½
a 2D0
ꢃ
ꢁ15.0 (c 0.2, CHCl3); Rf 0.21 (1:1 PhCH3–EtOAc); 1H NMR
a-L
(CDCl3, 600 MHz): d 8.16–7.43 (m, 25H, PhH), 5.53–4.96 (m, 10H,
5 ꢂ H-1, 5 ꢂ H4), 5.33 (dd, 1H, J 2.7, 10.1 Hz, H-3V), 4.51–4.18 (m,
5H, 5H-5), 4.07–3.82 (m, 9H, 5H-2, 4 ꢂ H-3), 3.69 (m, 1H, one pro-
ton of CH3(CH2)6CH2O), 3.51 (m, 1H, one proton of
CH3(CH2)6CH2O), 1.72 (s, 3H, CH3CO), 1.67–1.21 (m, 12H,
CH3(CH2)6CH2O), 1.15, 1.04, 0.70, 0.67, 0.54 (5d, each 3H, 15H,
5 ꢂ H-6), 0.87 (t, 3H, J 7.1 Hz, CH3(CH2)7O); 13C NMR (CDCl3,
150 MHz): d 167.6, 166.1, 133.8, 133.6, 133.2, 130.1, 130.0, 129.9,
129.8, 129.5, 129.4, 129.3, 129.1, 128.7, 128.7, 128.6, 128.5,
100.5, 99.9, 99.4, 98.9, 98.8, 79.5, 77.8, 77.5, 77.4, 773, 77.2, 77.1,
77.0, 76.9, 74.8, 72.9, 72.8, 72.7, 72.2, 72.1, 71.3, 68.8, 68.3, 67.9,
67.7, 67.0, 66.0, 65.8, 65.5, 65.3, 65.1, 64.6, 63.7, 31.9, 29.8, 29.7,
29.5, 29.4, 29.3, 26.2, 25.4, 22.7, 21.0, 16.2, 15.9, 15.8, 15.7, 14.2;
HRMALDIMS (positive ion): m/z 1445.5562 [M+Na]+ (Calcd
1445.5590).
a
-L
a
-L
a-L
a-L
a-L
Glycosylation of hexasaccharide 25 (225.8 mg, 0.11 mmol) with
12 (68.0 mg, 0.13 mmol) as described in Section 3.2.2 gave hepta-
saccharide 29 as a white foam (236.6 mg, 93.7%): ½a D20
ꢁ244.3 (c
ꢃ
1, CHCl3); Rf 0.38 (3:1 EtOAc–petroleum ether); 1H NMR (CDCl3,
600 MHz): d 8.04–6.69 (m, 70H, PhH), 5.67–4.88 (14d, 14H,
7 ꢂ H-1, 7 ꢂ H-4), 5.22 (dd, 1H, J 3.8, 10.4 Hz, H-3), 4.86, 4.66 (2d,
2 ꢂ 1H, J 11 Hz, PhCH2), 4.63–4.06 (m, 12H, 6 ꢂ PhCH2), 4.42–3.70
(m, 20H, 7H-5, 6H-3, 7H-2), 3.68 (m, 1H, one proton of
CH3(CH2)6CH2O), 3.51 (m, 1H, one proton of CH3(CH2)6CH2O), 1.72
(s, 3H, CH3CO), 1.67–1.78 (m, 14H, CH3(CH2)6CH2O), 1.15, 1.03,
0.72, 0.67, 0.65, 0.61, 0.53 (7d, each 3H, J 6.6 Hz, 21H, 7 ꢂ H-6),
0.88 (t, 3H, J 6.6 Hz, CH3(CH2)7O). 13C NMR (CDCl3, 150 MHz): d
182.3, 166.8, 166.7, 166.6, 166.4, 138.6, 138.5, 138.3, 138.1, 133.5,
133.4, 133.3, 133.1, 130.4, 130.3, 130.2, 130.1, 130.0, 128.8, 128.7,
128.6, 128.5, 128.3, 128.2, 127.8, 127.7, 127.4, 97.9, 93.5, 93.3,
93.2, 92.9, 92.8, 77.6, 77.4, 77.1, 74.5, 74.0, 73.8, 73.4, 73.0, 72.9,
72.8, 72.4, 71.2, 70.9, 70.8, 70.7, 70.6, 70.5, 70.4, 69.9, 68.8, 65.6,
65.4, 65.2, 65.1, 64.9, 64.4, 32.2, 30.0, 29.9, 29.7, 29.6, 26.5, 23.0,
21.0, 16.7, 16.5, 16.3, 16.2, 16.1, 15.8, 14.4; HRMALDIMS (positive
ion): m/z 2576.0531 [M+Na]+ (Calcd 2576.0541).
3.20. Octyl 3-O-acetyl-4-O-benzoyl-
O-benzoyl- -fucopyranosyl-(1?3)-4-O-benzoyl-
fucopyranosyl-(1?3)-4-O-benzoyl- -fucopyranosyl-(1?3)-4-
O-benzoyl- -fucopyranosyl-(1?3)-4-O-benzoyl-
fucopyranoside (32)
a-L-fucopyranosyl-(1?3)-4-
a-L
a-L-
a
-L
a-L
a-L-
Catalytic hydrogenolysis of compound 29 (35 mg, 0.0158 mmol)
as described in Section 3.2.4 gave 32 as a white foam (22 mg, 85%):
½
a 2D0
ꢃ
ꢁ230.8 (c 0.2, CHCl3); Rf 0.42 (1:1 PhCH3–EtOAc); 1H NMR
(CDCl3, 600 MHz): d 8.16–7.41 (m, 25H, PhH), 5.53–4.96 (12d,
12H, 6 ꢂ H-1, 6 ꢂ H4), 4.99 (dd, 1H, H-3VI), 4.52–4.18 (m, 6H, 5H-
5), 4.06–3.81 (m, 11H, 6H-2, 5H-3), 3.76 (m, 1H, one proton of
CH3(CH2)6CH2O), 3.56 (m, 1H, one proton of CH3(CH2)6CH2O), 1.91
(s, 3H, CH3CO), 1.60–1.24 (m, 12H, CH3(CH2)6CH2O), 0.93 (t, 3H, J
7.1 Hz, CH3(CH2)7O), 1.18, 1.08, 0.90, 0.89, 0.88, 0.83 (6d, each 3H,
18H, 6 ꢂ H-6); 13C NMR (CDCl3, 150 MHz): d 171.6, 170.9, 167.9,
167.8, 167.7, 167.6, 166.4, 134.1, 134.0, 133.9, 133.8, 133.8, 133.5,
130.4, 130.3, 130.2, 130.1, 129.8, 129.7, 129.6, 129.0, 128.9, 128.7,
100.8, 99.6, 99.1, 99.0, 79.7, 77.5, 77.3, 77.1, 73.2, 73.1, 73.0, 72.4,
71.6, 69.0, 68.6, 68.3, 68.2, 68.1, 68.0, 67.3, 66.3, 66.0, 65.8, 65.5,
65.3, 64.7, 38.4, 32.1, 31.5, 30.9, 30.0, 29.8, 29.7, 29.5, 26.5, 23.0,
3.18. Octyl 3-O-acetyl-4-O-benzoyl-2-O-benzyl-
osyl-(1?3)-4-O-benzoyl-2-O-benzyl- -fucopyranosyl-(1?3)-4-
O-benzoyl-2-O-benzyl- -fucopyrano-syl-(1?3)-4-O-benzoyl-
2-O-benzyl- -fucopyranosyl-(1?3)-4-O-benzoyl-2-O-benzyl-
-fucopyranosyl-(1?3)-4-O-benzoyl-2-O-benzyl- -fucopy-
ranosyl-(1?3)-4-O-benzoyl-2-O-benzyl- -fucopyranosyl-
(1?3)-4-O-benzoyl-2-O-benzyl- -fucopyranoside (30)
a-L-fucopyran-
a-L
a
-L
a
-L
a-L
a-L
a-L
a
-L
Glycosylation of acceptor 26 (100.5 mg, 0.042 mmol) with do-
nor 12 (45.6 mg, 0.084 mmol) as described in Section 3.2.2 gave
octasaccharide 30 as a white foam (74.5 mg, 63.8%): ½a D20
ꢁ285.1
ꢃ

1530
C. Zong et al. / Carbohydrate Research 345 (2010) 1522–1532
21.3, 21.2, 19.4, 16.5, 16.1, 15.9, 14.4, 14.0; HRMALDIMS (positive
CH3(CH2)5CH2CH2O), 1.25–1.32 (m, 2H, CH3(CH2)5CH2CH2O),
1.10–1.17 (m, 15H, 5 ꢂ H-6), 0.87 (t, 3H, J 6.9 Hz, CH3(CH2)7O);
13C NMR (CDCl3, 150 MHz) d 171.0, 167.9, 167.6, 166.3, 134.1,
133.9, 133.5, 131.2, 130.3, 130.1, 129.7, 129.6, 129.2, 129.0, 128.9,
128.8, 100.8, 99.6, 99.0, 79.7, 77.6, 77.5, 77.4, 77.3, 77.1, 73.2,
73.0, 72.9, 72.4, 72.1, 71.6, 69.0, 68.6, 68.2, 68.0, 67.3, 66.3, 66.0,
65.9, 65.6, 65.3, 51.1, 32.2, 32.1, 30.0, 29.8, 29.7, 29.6, 28.0, 26.6,
23.0, 21.2, 19.5, 16.5, 16.1, 15.9, 14.4; HRMALDIMS (positive ion):
m/z 1333.6493 [M+Na]+ (Calcd 1333.6459).
ion): m/z 1695.6403 [M+Na]+ (Calcd 1695.6405).
3.21. Octyl 3-O-acetyl-4-O-benzoyl-
O-benzoyl- -fucopyranosyl-(1?3)-4-O-benzoyl-
fucopyranosyl-(1?3)-4-O-benzoyl- -fucopyranosyl-(1?3)-4-
O-benzoyl- -fucopyranosyl-(1?3)-4-O-benzoyl-
fucopyranosyl-(1?3)-4-O-benzoyl- -fucopyranoside (33)
a-L-fucopyranosyl-(1?3)-4-
a-
L
a-L-
a
-L
a-
L
a-L-
a
-L
Catalytic hydrogenolysis of compound 29 (20 mg, 0.0069 mmol)
as described in Section 3.2.4 gave 33 as a white foam (13 mg, 87%):
3.24. Octyl 2-O-benzyl-
-fucopyranosyl-(1?3)-2-O-benzyl-
O-benzyl- -fucopyranosyl-(1?3)-2-O-benzyl-
fucopyranosyl-(1?3)-2-O-benzyl- -fucopyranoside (36)
a
-
L
-fucopyranosyl-(1?3)-2-O-benzyl-
a-
½
a 2D0
ꢃ
ꢁ155.9 (c 0.2, CHCl3); Rf 0.40 (1:1 PhCH3–EtOAc,); 1H NMR
L
a-L
-fucopyranosyl-(1?3)-2-
(CDCl3, 600 MHz): d 8.17–7.41 (m, 30H, PhH), 5.53–4.96 (14d,
14H, 7 ꢂ H-1, 7 ꢂ H4), 4.98 (dd, 1H, H-3VII), 4.52–4.18 (m, 7H,
7H-5), 4.06–3.81 (m, 13H, 7H2, 6H3), 3.76 (m, 1H, one proton of
CH3(CH2)6CH2O), 3.54 (m, 1H, one proton of CH3(CH2)6CH2O),
1.91 (s, 3H, CH3CO), 1.66–1.20 (m, 12H, CH3(CH2)6CH2O), 0.91 (t,
3H, J 7.1 Hz, CH3(CH2)7O), 1.17–0.80 (7d, each 3H, 21H, J 6.6 Hz,
7 ꢂ H-6); 13C NMR (CDCl3, 150 MHz): d 170.9, 167.8, 167.7,
167.6, 166.4, 139.7, 136.9, 134.1, 134.0, 133.9, 133.8, 133.5,
133.4, 130.3, 130.2, 130.1, 130.0, 129.8, 129.7, 129.6, 129.0,
128.9, 128.8, 128.7, 100.7, 99.6, 99.1, 99.0, 98.9, 79.7, 77.6, 77.5,
77.4, 77.3, 77.2, 77.1, 73.2, 73.1, 73.0, 72.9, 72.4, 71.6, 69.0, 68.5,
68.2, 68.1, 67.9, 67.3, 67.2, 66.3, 66.0, 65.8, 65.7, 65.5, 65.3, 32.1,
30.0, 29.9, 29.8, 29.7, 29.5, 26.5, 22.9, 21.2, 16.5, 16.2, 16.1, 16.0,
15.9, 14.4; HRMALDIMS (positive ion): m/z 1945.7244 [M+Na]+
(Calcd 1945.7288).
a
-L
a-L-
a-L
Debenzoylation of 25 (57.6 mg, 0.026 mmol) as described in the
preparation of 21 gave 36 (31.0 mg, 78%): ½a D20
ꢁ146.1 (c 0.2,
ꢃ
CHCl3); Rf 0.30 (20:1 CH2Cl2–MeOH,); 1H NMR (CDCl3, 600 MHz):
d
7.20–7.40 (m, 30H, PhH), 4.56–4.84 (m, 18H, 6 ꢂ H-1,
6 ꢂ PHCH2), 4.10 (m, 1H, 1H-5), 4.04 (m, 1H, 1H-5), 4.01 (dd, 1H,
J 3.3, 9.9 Hz, 1H-3), 3.91 (m, 9H, 5 ꢂ H-3, 4 ꢂ H-5), 3.73–3.85 (m,
6H, 6 ꢂ H-2), 3.67 (m, 2H, 2 ꢂ H-4), 3.40–3.64 (m, 6H, 4 ꢂ H-4,
CH3(CH2)6CH2O), 1.60 (m, 2H, CH3(CH2)5CH2CH2O), 1.25–1.35 (m,
13H, 3 ꢂ H-6, CH3(CH2)5CH2CH2O), 1.11–1.75 (m, 15H, 5 ꢂ H-6),
0.88 (t, 3H, J 7.1 Hz, CH3(CH2)7O); 13C NMR (CDCl3, 150 MHz) d
138.7, 137.8, 137.7, 137.6, 137.5, 137.4, 128.9, 128.8, 128.7,
128.6, 128.4, 128.3, 128.2, 128.1, 127.9, 127.7, 96.9, 94.2, 94.1,
94.0, 93.7, 77.4, 77.2, 76.9, 76.5, 75.2, 75.0, 74.9, 74.8, 74.7, 74.5,
74.4, 72.5, 72.1, 70.1, 68.4, 68.3, 68.2, 68.1, 66.3, 65.9, 65.7, 65.6,
64.8, 31.9, 29.8, 29.5, 29.4, 26.3, 22.8, 16.4, 16.3, 16.2, 16.1, 16.0,
14.2; HRMALDIMS (positive ion): m/z 1569.7542 [M+Na]+ (Calcd
1569.7526).
3.22. Octyl 3-O-acetyl-4-O-benzoyl-
O-benzoyl- -fucopyranosyl-(1?3)-4-O-benzoyl-
fucopyranosyl-(1?3)-4-O-benzoyl- -fucopyranosyl-(1?3)-4-
O-benzoyl- -fucopyranosyl-(1?3)-4-O-benzoyl-
fucopyranosyl-(1?3)-4-O-benzoyl- -fucopyranosyl-(1?3)-4-
O-benzoyl- -fucopyranoside (34)
a-L-fucopyranosyl-(1?3)-4-
a-
L
a-L-
a
-L
a-
L
a-L-
a
-L
a-
L
3.25. Octyl 2-O-sulfo-
fucopyranosyl-(1?3)-2-O-sulfo-
sulfo- -fucopyranoside (1)
a
-
L
-fucopyranosyl-(1?3)-2-O-sulfo-
a-L-
a-L
-fucopyranosyl-(1?3)-2-O-
Catalytic hydrogenolysis of compound 30 (20 mg, 0.0069 mmol)
as described in Section 3.2.4 gave 34 as a white foam (12 mg, 81%):
a-L
½
a 2D0
ꢃ
ꢁ283.7 (c 0.5, CHCl3); Rf 0.38 (1:1 PhCH3–EtOAc,); 1H NMR
The solution of tetraol 19 (18.4 mg, 0.0157 mmol) in DMF
(1 mL) was treated with sulfur trioxide–pyridine complex (12 mg,
0.072 mmol) at rt for 1 h, then the pH was adjusted to pH 9–10
with 3 N NaOH. The crude product was then purified by chroma-
tography on a column of Sephadex G-10. The appropriate fractions
were collected and condensed. Then the collection was dissolved in
0.4 N NaOH (1 mL) and stirred for 4 h at 40 °C. The mixture was
loaded on a G-10 column and washed with water. The appropriate
fractions were pooled and evaporated to afford 1 as an amorphous
(CDCl3, 600 MHz): d 8.15–7.41 (m, 40H, PhH), 5.52–4.97 (16d,
16H, 8 ꢂ H-1, 8 ꢂ H-4), 4.98 (dd, 1H, H-3VIII), 4.52–4.19 (m, 8H,
8H-5), 4.07–3.81 (m, 15H, 8H2, 7H3), 3.75 (m, 1H, one proton of
CH3(CH2)6CH2O), 3.54 (m, 1H, one proton of CH3(CH2)6CH2O),
1.91 (s, 3H, CH3CO), 1.67–1.22 (m, 12H, CH3(CH2)6CH2O), 1.17–
0.81 (8d, each 3H, 24H, J 6.6 Hz, 8 ꢂ H-6), 0.87 (t, 3H, J 7.1 Hz,
CH3(CH2)7O); 13C NMR (CDCl3, 150 MHz): d 170.9, 167.9, 167.8,
167.7, 166.4, 134.1, 134.0, 133.9, 133.8, 133.5, 130.4, 130.3,
130.2, 130.1, 129.9, 129.8, 129.7, 129.0, 128.9, 128.8, 128.7,
100.2, 99.6, 99.2, 99.1, 99.0, 79.7, 77.5, 77.4, 77.2, 77.1, 73.3,
73.2, 73.1, 73.0, 72.4, 72.0, 71.6, 70.7, 69.1, 68.6, 68.2, 68.0, 67.7,
67.3, 66.4, 66.1, 66.0, 65.8, 65.6, 65.4, 32.3, 32.1, 30.0, 29.9, 29.8,
29.7, 29.6, 26.5, 22.9, 16.5, 16.2, 16.1, 16.0, 15.9, 14.4; HRMALDIMS
(positive ion): m/z 2195.8086 [M+Na]+ (Calcd 2195.8067).
white solid (16.0 mg, 92%): ½a D20
ꢃ
ꢁ114.4 (c 0.6, H2O); 1H NMR
(CD3OD, 600 MHz): d 5.35 (d, 1H, J 3.3 Hz, H-1), 5.34 (d, 1H, J
3.3 Hz, H-1), 5.32 (d, 1H, J 3.8 Hz, H-1), 5.16 (d, 1H, J 3.9 Hz, H-1),
4.89 (m, 1H, H-2), 4.60 (dd, 1H, J 3.8, 9.9 Hz, H-2), 4.51–4.55 (m,
6H, 4 ꢂ H-5, 2 ꢂ H-2), 4.13–3.98 (m, 7H, 4 ꢂ H-3, 3 ꢂ H-4), 3.74
(d, 1H, J 2.8 Hz, H4), 3.64–3.51 (m, 2H, CH3(CH2)6CH2O), 1.64–
1.27 (m, 12H, CH3(CH2)6CH2O), 1.28–1.20 (m, 12H, 4 ꢂ H-6), 0.89
(t, 3H, J 7.1 Hz, CH3(CH2)7O); 13C NMR (CD3OD, 150 MHz): d 97.4,
94.7, 94.3, 93.7, 75.5, 73.9, 73.4, 73.0, 72.8, 68.9, 68.5, 68.3, 68.1,
67.7, 66.2, 65.7, 65.5, 31.7, 29.4, 29.3, 29.2, 29.1, 26.0, 22.4, 15.3,
3.23. Octyl 2-O-benzyl-
-fucopyranosyl-(1?3)-2-O-benzyl-
O-benzyl- -fucopyranosyl-(1?3)-2-O-benzyl-
fucopyranoside (35)
a
-
L
-fucopyranosyl-(1?3)-2-O-benzyl-
a-
L
a-L
-fucopyranosyl-(1?3)-2-
a-
L
a-L-
15.2, 13.1; HRESIMS calcd for
1145.1122, found 1145.1128.
C
32H54O29S4Na5 [M+Na]+
Debenzoylation of 24 (43 mg, 0.0229 mmol) as described in the
preparation of 21 gave 35 as a white foam (21.0 mg, 70%): ½a D20
ꢃ
3.26. Octyl 2-O-sulfo-
fucopyranosyl-(1?3)-2-O-sulfo-a-L
a
-
L
-fucopyranosyl-(1?3)-2-O-sulfo-
-fucopyranosyl-(1?3)-2-O-
-fucopyranos-yl-(1?3)-2-O-sulfo- -fucopyranoside
a-L-
ꢁ123.2 (c 0.6, CHCl3); Rf 0.39 (30:1 CH2Cl2–MeOH); 1H NMR (CDCl3,
600 MHz): d 7.20–7.40 (m, 25H, PhH), 4.91 (d, 1H, J 3.6 Hz, H-1),
4.81 (m, 3H, 3H-1), 4.75 (d, 1H, J 2.8 Hz, H-1), 4.52–4.91 (m, 10H,
PHCH2), 4.10 (m, 2H, 2 ꢂ H-5,), 4.01 (m, 3H, H-5, 2 ꢂ H-4), 3.91
(m, 5H, 2 ꢂ H-5, 3 ꢂ H-4), 3.76–3.84 (m, 4H, 1 ꢂ H-3, 3 ꢂ H-2),
3.40–3.67 (m, 6H, 4 ꢂ H-3, CH3(CH2)6CH2O), 1.59 (m, 2H,
sulfo-a-
L
a-L
(2)
Sulfation of 31 (26 mg, 0.0183 mmol) as described in the prep-
aration of 1 gave 2 as an amorphous white solid (23.0 mg, 92%):

C. Zong et al. / Carbohydrate Research 345 (2010) 1522–1532
1531
½
a 2D0
ꢃ
ꢁ95.1 (c 0.6, H2O); 1H NMR (D2O, 500 MHz): d 5.32 (m, 4H,
HRESIMS calcd for C56H90O57S8Na8 [Mꢁ3Na]3ꢁ 681.7132, found
4 ꢂ H-1), 5.13 (d, 1H, J 3.3 Hz, H-1), 4.55–4.42 (m, 10H, 5 ꢂ H-2,
4 ꢂ H-5), 4.09 (m, 9H, 5 ꢂ H-3, 4 ꢂ H-4, H-5), 3.58 (d, J 3.0 Hz,
1H, H-4), 3.54–3.64 (m, 2H, CH3(CH2)6CH2O), 1.64–1.34 (m, 12H,
CH3(CH2)6CH2O), 1.24 (m, 15H, 5 ꢂ H-6), 0.85 (t, 3H, J 7.1 Hz,
CH3(CH2)7O); 13C NMR (D2O, 125 MHz): d 96.6, 95.2, 94.5, 75.4,
74.1, 73.4, 73.2, 72.3, 69.4, 69.2, 69.1, 68.9, 67.5, 67.0, 66.8, 66.3,
34.7, 31.3, 28.6, 25.4, 22.2, 15.5, 15.4, 13.6; HRESIMS calcd for
681.7108.
3.30. Octyl 3,4-di-O-sulfo-
-fucopyranosyl-(1?3)-4-O-sulfo-
4-O-sulfo- -fucopyranoside (6)
a
-
L
-fucopyranosyl-(1?3)-4-O-sulfo-
a-
L
a-L
-fucopyranosyl-(1?3)-
a-L
A solution of 21 (20 mg, 0.0186 mmol) in DMF (1 mL) was trea-
ted with SO3ꢀPyr (59.2 mg, 0.372 mmol) at rt for 1 h, and then the
pH was adjusted to pH 9–10 with 3 N NaOH. The crude product
was then purified by chromatography on a column of G-10. The
appropriate fractions were collected and condensed. To a solution
of the crude product in 1:1 H2O–MeOH (20 mL) was added 10% Pd/
C catalyst (400 mg). The mixture was degassed, and the flask was
filled with H2. The mixture was stirred for 12 h at 40 °C. Pd/C
was separated by filtration through a Celite pad and concentrated.
Column chromatography (G-10) of the residue gave 6 as an amor-
C
38H63O36S5Na5 [Mꢁ2Na]2ꢁ 662.0698, found 662.0707.
3.27. Octyl 2-O-sulfo-
fucopyranosyl-(1?3)-2-O-sulfo-
sulfo- -fucopyranos-yl-(1?3)-2-O-sulfo-
(1?3)-2-O-sulfo- -fucopyranoside (3)
a-
L
-fucopyranosyl-(1?3)-2-O-sulfo-
-fucopyranosyl-(1?3)-2-O-
-fucopyranosyl-
a-L-
a
-L
a
-L
a-L
a-L
Sulfation of 32 (50 mg, 0.024 mmol) as described in the prepa-
ration of 1 gave 3 as an amorphous white solid (20 mg, 87%): ½a D20
ꢃ
ꢁ116.8 (c 0.6, H2O); 1H NMR (D2O, 600 MHz): d 5.33 (m, 5H, 5 ꢂ H-
1), 5.17 (d, J 3.67 Hz, 1H, H-1), 4.63–4.52 (m, 5H, 5H-2), 4.43 (m,
6H, 5H-5, 1H-2), 4.09 (m, 11H, 5 ꢂ H3, 5 ꢂ H4, H-5), 4.00 (dd, J
2.3, 10.6 Hz, 1H, H-3), 3.88 (d, 1H, J 3.2 Hz, H-4), 3.68–3.58 (m,
2H, CH3(CH2)6CH2O), 1.64–1.28 (m, 12H, CH3(CH2)6CH2O), 1.23
(m, 18H, 6 ꢂ H-6), 0.85 (t, 3H, CH3(CH2)7O); 13C NMR (D2O,
150 MHz): d 96.8, 95.9, 75.4, 74.0, 73.9, 73.3, 72.7, 72.4, 69.3,
69.2, 69.1, 69.0, 67.6, 67.0, 66.7, 66.3, 34.8, 31.2, 28.6, 28.5, 25.9,
25.5, 22.1, 15.5, 15.4, 13.5; HRESIMS calcd for C44H72O43S6Na6
[Mꢁ2Na]2ꢁ 786.0681, found 786.0652.
phous white solid (18 mg, 82%): ½a D20
ꢃ
ꢁ121.2 (c 0.3, H2O); 1H NMR
(D2O, 600 MHz): d 5.16, 5.13, 5.11, 4.91 (4d, 4H, 4 ꢂ H-1), 4.87 (d,
1H, J 2.3 Hz, H-3IV), 4.74 (m, 3H, 3 ꢂ H-3), 4.40–4.53 (3 m, 3H,
3 ꢂ H-5), 4.15 (m, 1H, H-5), 4.04 (m, 3H, 3 ꢂ H-3), 3.90 (m, 4H,
4 ꢂ H-4), 3.55–3.67 (m, 2H, CH3(CH2)6CH2O), 1.64–1.27 (m, 12H,
CH3(CH2)6CH2O), 1.28–1.20 (m, 12H, 4 ꢂ H-6), 0.86 (t, 3H, J
7.1 Hz, CH3(CH2)7O); 13C NMR (D2O, 150 MHz): d 99.0, 98.7, 98.1,
80.0, 79.8, 79.6, 76.8, 76.4, 76.1, 76.0, 69.0, 67.7, 67.1, 66.6, 35.0,
30.6, 30.5, 30.4, 29.1, 28.9, 25.9, 22.5, 16.3, 16.2, 16.1, 13.9; HRE-
SIMS calcd for
589.0417.
C
32H53O32S5Na5 [Mꢁ2Na]2ꢁ 589.0408, found
3.28. Octyl 2-O-sulfo-
fucopyranosyl-(1?3)-2-O-sulfo-
sulfo- -fucopyranosyl-(1?3)-2-O-sulfo-
(1?3)-2-O-sulfo- -fucopyranosyl-(1?3)-2-O-sulfo-
fucopyranoside (4)
a
-
L
-fucopyranosyl-(1?3)-2-O-sulfo-
-fucopyranosyl-(1?3)-2-O-
-fucopyranosyl-
a-L-
a
-L
3.31. Octyl 3,4-di-O-sulfo-
-fucopyranosyl-(1?3)-4-O-sulfo-
4-O-sulfo- -fucopyranosyl-(1?3)-4-O-sulfo-
fucopyranoside (7)
a
-
L
-fucopyranosyl-(1?3)-4-O-sulfo-
a
-L
a-L
a-
L
a-L
-fucopyranosyl-(1?3)-
a-
L
a
-L
-
a-
L
a-L-
Sulfation of 33 (24.5 mg, 0.0127 mmol) as described in the
preparation of 1 gave 4 as an amorphous white solid (20 mg,
Sulfation of 35 (22 mg, 0.0168 mmol) as described in the prep-
aration of 6 gave 7 (22.0 mg, 89%): ½a D20
ꢃ
ꢁ62.8 (c 0.1, H2O); 1H NMR
83%): ½a 2D0
ꢃ
ꢁ108.7 (c 0.6, H2O); 1H NMR (D2O, 600 MHz): d 5.33
(D2O, 600 MHz): d 5.16 (d, 1H, J 3.6 Hz, H-1), 5.21 (m, 3H, 3 ꢂ H-1),
5.01 (d, 1H, J 3.6 Hz, H-1), 4.97 (d, 1H, J 2.7 Hz, H-4V), 4.85 (m, 4H,
4 ꢂ H-4), 4.72 (m, 1H, H-3V), 4.40–4.53 (m, 3H, 3 ꢂ H-5), 4.14 (m,
1H, H-5), 3.99–4.09 (m, 5H, 1H-5, 4 ꢂ H-3), 3.92 (m, 5H, 5 ꢂ H-
2), 3.53–3.69 (m, 2H, CH3(CH2)6CH2O), 1.61 (m, 2H,
(m, 6H, 6 ꢂ H-1), 5.17 (d, J 3.7 Hz, 1H, H-1), 4.63–4.52 (m, 6H,
6H-2), 4.43 (m, 7H, 6H-5, 1H-2), 4.09 (m, 13H, 6 ꢂ H-3, 6 ꢂ H-4,
H-5), 4.00 (dd, J 3.2, 10.6 Hz, 1H, H-3), 3.88 (d, 1H, J 2.7 Hz, H-4),
3.68–3.58 (m, 2H, CH3(CH2)6CH2O), 1.64–1.28 (m, 12H,
CH3(CH2)6CH2O), 1.23 (m, 21H, 7 ꢂ H-6), 0.85 (t, 3H, J 7.1 Hz,
CH3(CH2)7O); 13C NMR (D2O, 150 MHz): d 95.1, 94.1, 75.4, 74.0,
73.9, 73.6, 73.3, 72.4, 69.4, 69.2, 69.1, 69.0, 67.0, 66.7, 66.3, 31.2,
30.1, 28.7, 28.6, 25.5, 22.2, 15.6, 15.5, 15.4, 13.6; HRESIMS calcd
for C50H81O50S7Na7 [Mꢁ3Na]3ꢁ 599.0477, found 599.0461.
CH3(CH2)5CH2CH2O),
1.24–1.30
(m,
25H,
5 ꢂ H-6,
CH3(CH2)5CH2CH2O), 0.95 (t, 3H, J 6.4 Hz, CH3(CH2)7O); 13C NMR
(D2O, 150 MHz): d 99.1, 99.0, 98.8, 98.1, 98.0, 80.2, 80.1, 80.0,
79.9, 79.8, 79.7, 79.5, 76.8, 76.7, 76.4, 76.0, 75.9, 69.0, 67.6, 67.2,
67.0, 66.9, 66.6, 31.6, 29.1, 28.9, 25.9, 22.5, 16.3, 16.2, 16.1, 13.9;
HRESIMS calcd for C38H62O39S6Na7 [M+Na]+ 1495.0476, found
1495.0425.
3.29. Octyl 2-O-sulfo-a-L-fucopyranosyl-(1?3)-2-O-sulfo-a-L-
fucopyranosyl-(1?3)-2-O-sulfo-
a
-
L
-fucopyranosyl-
-fucopyranosyl-(1?3)-2-O-
-fucopyranosyl-
-fucopyranosyl-(1?3)-2-O-sulfo-
fucopyranosyl-(1?3)-2-O-sulfo-
a
-L
3.32. Octyl 3,4-di-O-sulfo-
-fucopyranosyl-(1?3)-4-O-sulfo-
4-O-sulfo- -fucopyranosyl-(1?3)-4-O-sulfo-
fucopyranosyl-(1?3)-4-O-sulfo- -fucopyranoside (8)
a-
L-fucopyranosyl-(1?3)-4-O-sulfo-
sulfo-
(1?3)-2-O-sulfo-
fucopyranoside (5)
a
-
L
-fucopyranosyl-(1?3)-2-O-sulfo-
a-L
a-
L
a-L
-fucopyranosyl-(1?3)-
a-
L
a
-L
-
a-
L
a-L-
a-L
Sulfation of 34 (21.0 mg, 0.0097 mmol) as described in the
preparation of 1 gave 5 as an amorphous white solid (14 mg,
Sulfation of 36 (22 mg, 0.0143 mmol) as described in the prep-
aration of 6 gave 8 (23.0 mg, 94%): ½a D20
ꢃ
ꢁ20.9 (c 0.3, H2O); 1H NMR
69%): ½a 2D0
ꢃ
ꢁ112.1 (c 0.3, H2O); 1H NMR (D2O, 600 MHz): d 5.33
(D2O, 600 MHz): d 5.11 (m, 5H, 5 ꢂ H-1), 4.91 (d, 1H, J 3.6 Hz, H-1I),
4.87 (d, 1H, J 2.7 Hz, H-4IV), 4.76 (m, 5H, 5 ꢂ H-4), 4.60 (m, 1H, H-
3IV), 4.41–4.51 (m, 5H, 5 ꢂ H-5), 4.15 (m, 1H, H-5), 3.99–4.09 (m,
5H, 5 ꢂ H-3), 3.95 (dd, 1H, J 3.6, 10.1 Hz, H-2), 3.88 (m, 5H,
5 ꢂ H-2), 3.53–3.69 (m, 2H, CH3(CH2)6CH2O), 1.61 (m, 2H,
(m, 6H, 6 ꢂ H-1), 5.18 (d, J 4.1 Hz, 1H, H-1), 4.56–4.52 (m, 7H,
7H-2), 4.44 (m, 8H, 7H-5, 1H-2), 4.09 (m, 15H, 7 ꢂ H-3, 7 ꢂ H-4,
1H-5), 4.00 (dd, J 2.8, 10.6 Hz, 1H, H-3), 3.88 (d, 1H, J 3.7 Hz, H-
4), 3.68–3.58 (m, 2H, CH3(CH2)6CH2O), 1.64–1.28 (m, 12H,
CH3(CH2)6CH2O), 1.23 (m, 24H, 24 ꢂ H-6), 0.85 (t, 3H, J 7.1 Hz,
CH3(CH2)7O); 13C NMR (D2O, 150 MHz): d 96.7, 95.3, 95.2, 95.1,
94.5, 75.4, 74.3, 74.2, 74.1, 73.4, 73.2, 72.3, 69.5, 69.3, 69.1, 69.9,
67.5, 67.1, 66.7, 66.4, 34.7, 31.3, 28.6, 25.5, 22.2, 15.5, 15.4, 13.6;
CH3(CH2)5CH2CH2O),
1.24–1.30
(m,
28H,
6 ꢂ H-6,
CH3(CH2)5CH2CH2O), 0.95 (t, 3H, J 6.9 Hz, CH3(CH2)7O); 13C NMR
(D2O, 150 MHz) d 99.1, 99.0, 98.8, 98.7, 98.1, 98.0, 80.3, 80.0,
79.9, 76.8, 76.7, 76.1, 76.0, 69.1, 67.7, 67.6, 67.2, 67.1, 67.0, 66.6,

1532
C. Zong et al. / Carbohydrate Research 345 (2010) 1522–1532
6. Ghosh, T.; Chattopadhyay, K.; Marschall, M.; Karmarkar, P.; Mandal, P.; Ray, B.
Glycobiology 2009, 19, 2–15.
7. Boisson-Vidal, C.; Chaubet, F.; Chevolot, L.; Sinquin, C.; Theveniaux, J.; Millet, J.;
Sternberg, C.; Mulloy, B.; Fischer, A. M. Drug Dev. Res. 2000, 51, 216–224.
8. Nakayasu, S.; Soegima, R.; Yamaguchi, K.; Oda, T. Biosci. Biotechnol. Biochem.
2009, 73, 961–964.
31.6, 29.1, 28.9, 25.9, 22.5, 16.3, 16.2, 16.1, 16.0, 13.9; HRESIMS
calcd for C44H71O46S7Na8 [M+2Na]2+ 883.0171, found 883.0197.
Acknowledgment
9. Gerbst, A. G.; Ustuzhanina, N. E.; Grachev, A. A.; Khatuntseva, E. A.; Tsvetkov, D.
E.; Whitfield, D. M.; Berces, A.; Nifantiev, N. E. J. Carbohydr. Chem. 2001, 20,
821–831.
10. Gerbst, A. G.; Ustuzhanina, N. E.; Grachev, A. A.; Zlotina, N. S.; Khatuntseva, E.
A.; Tsvetkov, D. E.; Shashkov, A. S.; Usov, A. I.; Nifantiev, N. E. J. Carbohydr.
Chem. 2002, 2, 313–324.
This work is supported by the National Basic Research Program
of China (2003CB716400).
Supplementary data
11. Ustyuzhanina, N.; Krylov, V.; Grachev, A.; Gerbst, A.; Nifantiev, N. Synthesis
2006, 23, 4017–4031.
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.carres.2010.04.006.
12. Hua, Y.-X.; Gu, G.-F.; Du, Y.-G. Carbohydr. Res. 2004, 339, 867–872.
13. (a) Logeart, D.; Prigent-Richard, S.; Boisson-Vidal, C.; Charbet, F.; Durand, P.;
Jozefonvicz, J.; Letourneur, D. Eur. J. Cell Biol. 1997, 74, 385–390; (b) Koyanagi,
S.; Tanigawa, N.; Nakagawa, H.; Soeda, S.; Shimeno, H. Biochem. Pharmacol.
2003, 65, 173–179; (c) Cumashi, A.; Hshakova, N. A.; Preobrazhenshaya, M. E.,
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